Is IFT172 p.Glu645= (c.1935G>A) pathogenic?

IFT172 p.Glu645= (c.1935G>A) is classified Likely benign in IFT172 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-01). Very rare (popmax 0.000678%, nfe); Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

How common is IFT172 p.Glu645= (c.1935G>A) in the general population?

IFT172 p.Glu645= (c.1935G>A) is very rare (popmax 0.000678%, nfe) (gnomAD).

IFT172 p.Glu645=

Q: What condition is associated with IFT172 p.Glu645= (c.1935G>A)?

IFT172 p.Glu645= (c.1935G>A) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

c.1935G>A · rs755341436 · VCV1152301

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

short-rib thoracic dysplasia 10 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP 2.1, phastCons 1
Overall
CADD	11.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,564 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,548 alleles · very rare exomes 7/1,461,364 · genomes 1/152,184 · 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.Glu645=
Coding: c.1935G>A
MANE Select: NM_015662
dbSNP: rs755341436
Type: single nucleotide variant
Location: chr2:27465413 (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.Glu645Gln Uncertain significance ★ ⚠ same residue
IFT172 p.Glu645Val 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-glu645 (accessed [today's date]).

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