Is IFT172 p.Asp183Val (c.548A>T) pathogenic?

IFT172 p.Asp183Val (c.548A>T) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-26). AlphaMissense: ambiguous (0.5214); Very rare (popmax 0.00223%, eas); Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

How common is IFT172 p.Asp183Val (c.548A>T) in the general population?

IFT172 p.Asp183Val (c.548A>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about IFT172 p.Asp183Val (c.548A>T)?

AlphaMissense predicts ambiguous (score 0.5214) — an in-silico prediction, not a clinical call.

IFT172 p.Asp183Val

Q: What condition is associated with IFT172 p.Asp183Val (c.548A>T)?

IFT172 p.Asp183Val (c.548A>T) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71, Bardet-Biedl syndrome 20 (ClinVar).

c.548A>T · VCV3586375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5214 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

short-rib thoracic dysplasia 10 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.5214	ambiguous
REVEL	0.407	indeterminate
SaProt	LLR -7.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	26.6	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 0.00223% East Asian · 1/44,824 alleles

Overall 0.000125% 2/1,600,304 alleles · very rare exomes 1/1,448,150 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,824
African / African-American	0.00134%	74,656

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.Asp183Val
Coding: c.548A>T
MANE Select: NM_015662
Type: single nucleotide variant
Location: chr2:27483311 (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 Bardet-Biedl syndrome 20

Similar variants

IFT172 p.Asp183= 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
IFT172 c.3821+1G>A Pathogenic/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-asp183val (accessed [today's date]).

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