Is IFT172 p.Pro1685Ser (c.5053C>T) pathogenic?

IFT172 p.Pro1685Ser (c.5053C>T) is classified Uncertain significance in IFT172 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-24). AlphaMissense: ambiguous (0.3545); Ultra-rare (popmax 0.0117%, amr); Associated with retinitis pigmentosa 71.

What condition is associated with IFT172 p.Pro1685Ser (c.5053C>T)?

IFT172 p.Pro1685Ser (c.5053C>T) is associated with retinitis pigmentosa 71, short-rib thoracic dysplasia 10 with or without polydactyly, Bardet-Biedl syndrome 20 (ClinVar).

How common is IFT172 p.Pro1685Ser (c.5053C>T) in the general population?

IFT172 p.Pro1685Ser (c.5053C>T) is ultra-rare (popmax 0.0117%, amr) (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.Pro1685Ser (c.5053C>T)?

AlphaMissense predicts ambiguous (score 0.3545) — an in-silico prediction, not a clinical call.

IFT172 p.Pro1685Ser

c.5053C>T · rs775285304 · VCV1461096

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3545 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

retinitis pigmentosa 71

Computational evidence

Protein change
AlphaMissense	0.3545	ambiguous
REVEL	0.295	indeterminate
SaProt	LLR -5.97	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 9,675 bp · p 0.0028 · regional, not allelic
Overall
CADD	26.0	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 0.0117% Admixed American · 7/59,934 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000806% 13/1,612,728 alleles · ultra-rare exomes 11/1,460,618 · genomes 2/152,110 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,562
Remaining individualsnot grpmax-eligible	0.00481%	20,797
European (non-Finnish)	0.000254%	393,144

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.Pro1685Ser
Coding: c.5053C>T
MANE Select: NM_015662
dbSNP: rs775285304
Type: single nucleotide variant
Location: chr2:27445311 (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 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 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
IFT172 c.786-2A>G 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-pro1685ser (accessed [today's date]).

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