Is IFT172 p.Pro1638= (c.4914G>A) pathogenic?

IFT172 p.Pro1638= (c.4914G>A) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). Very rare (popmax 0.00401%, afr); Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

How common is IFT172 p.Pro1638= (c.4914G>A) in the general population?

IFT172 p.Pro1638= (c.4914G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

IFT172 p.Pro1638=

Q: What condition is associated with IFT172 p.Pro1638= (c.4914G>A)?

IFT172 p.Pro1638= (c.4914G>A) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

c.4914G>A · rs374531022 · VCV1394843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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	Δ0.83	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.71	loss · gain 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.23	GERP 0.14, phastCons 0.98
Overall
CADD	19.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,898 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000496% 8/1,614,052 alleles · very rare exomes 4/1,461,876 · genomes 4/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,966
South Asian	0.00329%	30,363
European (non-Finnish)	0.000169%	590,019

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.Pro1638=
Coding: c.4914G>A
MANE Select: NM_015662
dbSNP: rs374531022
Type: single nucleotide variant
Location: chr2:27445745 (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.Pro1638Ser Uncertain significance ★ ⚠ same residue
IFT172 p.Pro1638Leu 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-pro1638 (accessed [today's date]).

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