Is IFT172 p.Ser1673Phe (c.5018C>T) pathogenic?

IFT172 p.Ser1673Phe (c.5018C>T) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). AlphaMissense: likely pathogenic (0.7733); Very rare (popmax 0.00134%, afr); Associated with retinitis pigmentosa 71.

What condition is associated with IFT172 p.Ser1673Phe (c.5018C>T)?

IFT172 p.Ser1673Phe (c.5018C>T) is associated with retinitis pigmentosa 71, short-rib thoracic dysplasia 10 with or without polydactyly (ClinVar).

How common is IFT172 p.Ser1673Phe (c.5018C>T) in the general population?

IFT172 p.Ser1673Phe (c.5018C>T) is very rare (popmax 0.00134%, afr) (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.Ser1673Phe (c.5018C>T)?

AlphaMissense predicts likely pathogenic (score 0.7733) — an in-silico prediction, not a clinical call.

IFT172 p.Ser1673Phe

c.5018C>T · rs767672341 · VCV2060654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

retinitis pigmentosa 71

Computational evidence

Protein change
AlphaMissense	0.7733	likely pathogenic
REVEL	0.629	indeterminate
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
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	26.3	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 0.00134% African / African-American · 1/74,866 alleles

Overall 6.2e-05% 1/1,613,354 alleles · very rare exomes 0/1,461,298 · genomes 1/152,056 · 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.Ser1673Phe
Coding: c.5018C>T
MANE Select: NM_015662
dbSNP: rs767672341
Type: single nucleotide variant
Location: chr2:27445346 (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 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-ser1673phe (accessed [today's date]).

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