Is IFT172 p.Arg136His (c.407G>A) pathogenic?

IFT172 p.Arg136His (c.407G>A) is classified Uncertain significance in IFT172 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-22). AlphaMissense: likely pathogenic (0.8408); Very rare (popmax 0.00329%, sas); Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

How common is IFT172 p.Arg136His (c.407G>A) in the general population?

IFT172 p.Arg136His (c.407G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about IFT172 p.Arg136His (c.407G>A)?

AlphaMissense predicts likely pathogenic (score 0.8408) — an in-silico prediction, not a clinical call.

IFT172 p.Arg136His

Q: What condition is associated with IFT172 p.Arg136His (c.407G>A)?

IFT172 p.Arg136His (c.407G>A) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

c.407G>A · rs763923637 · VCV1035649

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8408 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short-rib thoracic dysplasia 10 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.8408	likely pathogenic
REVEL	0.697	pathogenic-leaning
SaProt	LLR -10.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.4, 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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00329% South Asian · 3/91,072 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.0013% 21/1,613,870 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,357
Remaining individualsnot grpmax-eligible	0.0032%	31,241
East Asian	0.00223%	44,894
African / African-American	0.00134%	74,884
European (non-Finnish)	0.00119%	84,286

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.Arg136His
Coding: c.407G>A
MANE Select: NM_015662
dbSNP: rs763923637
Type: single nucleotide variant
Location: chr2:27483655 (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.Arg136Cys Uncertain significance ★★ ⚠ same residue
IFT172 p.Arg136= 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

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-arg136his (accessed [today's date]).

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