Is IFT172 p.Ala82Ser (c.244G>T) pathogenic?

IFT172 p.Ala82Ser (c.244G>T) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-11). AlphaMissense: ambiguous (0.4465); Very rare (popmax 0.00017%, nfe); Associated with retinitis pigmentosa 71.

What condition is associated with IFT172 p.Ala82Ser (c.244G>T)?

IFT172 p.Ala82Ser (c.244G>T) is associated with retinitis pigmentosa 71, short-rib thoracic dysplasia 10 with or without polydactyly (ClinVar).

How common is IFT172 p.Ala82Ser (c.244G>T) in the general population?

IFT172 p.Ala82Ser (c.244G>T) is very rare (popmax 0.00017%, nfe) (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.Ala82Ser (c.244G>T)?

AlphaMissense predicts ambiguous (score 0.4465) — an in-silico prediction, not a clinical call.

IFT172 p.Ala82Ser

c.244G>T · rs1398648274 · VCV2038022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4465 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

retinitis pigmentosa 71

Computational evidence

Protein change
AlphaMissense	0.4465	ambiguous
REVEL	0.615	indeterminate
SaProt	LLR -12.65	damaging
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,177,652 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,610,412 alleles · very rare exomes 2/1,459,396 · genomes 0/151,016 · joint denominator

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.Ala82Ser
Coding: c.244G>T
MANE Select: NM_015662
dbSNP: rs1398648274
Type: single nucleotide variant
Location: chr2:27485070 (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: short-rib thoracic dysplasia 10 with or without polydactyly

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.Ala82= Likely benign ★ 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-ala82ser (accessed [today's date]).

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