Is IFT172 p.Ile83Val (c.247A>G) pathogenic?

IFT172 p.Ile83Val (c.247A>G) is classified Uncertain significance in IFT172 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-12-18). AlphaMissense: likely benign (0.054); Ultra-rare (popmax 0.0329%, mid); Associated with retinitis pigmentosa 71.

What condition is associated with IFT172 p.Ile83Val (c.247A>G)?

IFT172 p.Ile83Val (c.247A>G) is associated with retinitis pigmentosa 71, optic atrophy, short-rib thoracic dysplasia 10 with or without polydactyly (ClinVar).

How common is IFT172 p.Ile83Val (c.247A>G) in the general population?

IFT172 p.Ile83Val (c.247A>G) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IFT172 p.Ile83Val (c.247A>G)?

AlphaMissense predicts likely benign (score 0.054) — an in-silico prediction, not a clinical call.

IFT172 p.Ile83Val

c.247A>G · rs142227350 · VCV649133

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.054 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 71

Computational evidence

Protein change
AlphaMissense	0.054	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	9.355	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,078 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00899%

Overall 0.00466% 75/1,610,490 alleles · ultra-rare exomes 63/1,458,766 · genomes 12/151,724 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,039
Admixed American	0.02%	4,994
Remaining individualsnot grpmax-eligible	0.0144%	6,929
East Asian	0.00446%	22,424
European (non-Finnish)	0.00425%	23,544

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: IFT172
Protein: p.Ile83Val
Coding: c.247A>G
MANE Select: NM_015662
dbSNP: rs142227350
Type: single nucleotide variant
Location: chr2:27485067 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.98 · 1 PDB

Full IFT172 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 71 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: optic atrophy short-rib thoracic dysplasia 10 with or without polydactyly Bardet-Biedl syndrome 20

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

IFT172 p.Ile83Met Uncertain significance ★ same residue
IFT172 c.1411+2T>C Likely pathogenic ★★ same condition
IFT172 c.1525-1G>A Pathogenic/Likely pathogenic ★★ same condition
IFT172 c.184-2A>C Likely pathogenic ★★ same condition
IFT172 c.2443-1G>C Likely pathogenic ★★ same condition
IFT172 c.2976-2A>T Likely pathogenic ★★ same condition
IFT172 c.3111+1G>T Likely pathogenic ★★ same condition
IFT172 c.3821+1G>A Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ift172-p-ile83val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown