Is IFT172 p.Ala841= (c.2523G>A) pathogenic?

IFT172 p.Ala841= (c.2523G>A) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-03-08). Ultra-rare (popmax 0.033%, mid); Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

How common is IFT172 p.Ala841= (c.2523G>A) in the general population?

IFT172 p.Ala841= (c.2523G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

IFT172 p.Ala841=

Q: What condition is associated with IFT172 p.Ala841= (c.2523G>A)?

IFT172 p.Ala841= (c.2523G>A) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

c.2523G>A · rs201637357 · VCV2140694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

short-rib thoracic dysplasia 10 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.82	acceptor gain · deltas
Pangolin	Δ0.70	gain · loss 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -2.7	GERP -5
Overall
CADD	18.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00273% 44/1,610,854 alleles · ultra-rare exomes 33/1,458,586 · genomes 11/152,268 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0378%	2,644
Middle Easterngrpmax	0.033%	3,031
East Asian	0.00668%	14,960
African / African-American	0.00533%	18,756
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,482
South Asian	0.0011%	91,076
European (non-Finnish)	0.000763%	131,110

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala841=
Coding: c.2523G>A
MANE Select: NM_015662
dbSNP: rs201637357
Type: single nucleotide variant
Location: chr2:27459828 (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.Ala841Val Uncertain significance ★★ ⚠ same residue
IFT172 p.Ala841Thr 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-ala841 (accessed [today's date]).

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