Is IFT172 p.Arg367Ser (c.1099C>A) pathogenic?

IFT172 p.Arg367Ser (c.1099C>A) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). AlphaMissense: ambiguous (0.4694); Very rare (popmax 6.84e-05%); Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

How common is IFT172 p.Arg367Ser (c.1099C>A) in the general population?

IFT172 p.Arg367Ser (c.1099C>A) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about IFT172 p.Arg367Ser (c.1099C>A)?

AlphaMissense predicts ambiguous (score 0.4694) — an in-silico prediction, not a clinical call.

IFT172 p.Arg367Ser

Q: What condition is associated with IFT172 p.Arg367Ser (c.1099C>A)?

IFT172 p.Arg367Ser (c.1099C>A) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

c.1099C>A · rs755816980 · VCV2931462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

short-rib thoracic dysplasia 10 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.4694	ambiguous
REVEL	0.518	indeterminate
SaProt	LLR -8.52	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	23.1	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 6.84e-05%

Overall 6.84e-05% 1/1,461,890 alleles · very rare

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.Arg367Ser
Coding: c.1099C>A
MANE Select: NM_015662
dbSNP: rs755816980
Type: single nucleotide variant
Location: chr2:27478063 (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

short-rib thoracic dysplasia 10 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 71

Similar variants

IFT172 p.Arg367Cys Uncertain significance ★★ ⚠ same residue
IFT172 p.Arg367His 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

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-arg367ser (accessed [today's date]).

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