Is IFT172 p.Val482Ile (c.1444G>A) pathogenic?

IFT172 p.Val482Ile (c.1444G>A) is classified Conflicting classifications of pathogenicity in IFT172 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-17). AlphaMissense: likely benign (0.06); Very rare (popmax 0.00653%, nfe); Associated with Inborn genetic diseases.

What condition is associated with IFT172 p.Val482Ile (c.1444G>A)?

IFT172 p.Val482Ile (c.1444G>A) is associated with Inborn genetic diseases, short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

How common is IFT172 p.Val482Ile (c.1444G>A) in the general population?

IFT172 p.Val482Ile (c.1444G>A) is very rare (popmax 0.00653%, nfe) (gnomAD).

What do computational predictors say about IFT172 p.Val482Ile (c.1444G>A)?

AlphaMissense predicts likely benign (score 0.06) — an in-silico prediction, not a clinical call.

IFT172 p.Val482Ile

c.1444G>A · rs771104054 · VCV851128

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.06 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00653%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.06	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -5.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.68, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	14.29	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 0.00653% European (non-Finnish) · 77/1,179,966 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00533% 86/1,613,924 alleles · very rare exomes 85/1,461,762 · genomes 1/152,162 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00653%	15,324
Remaining individualsnot grpmax-eligible	0.0064%	15,622
East Asian	0.00446%	22,446
African / African-American	0.00267%	37,457
Admixed American	0.00167%	59,972

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.Val482Ile
Coding: c.1444G>A
MANE Select: NM_015662
dbSNP: rs771104054
Type: single nucleotide variant
Location: chr2:27472330 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: short-rib thoracic dysplasia 10 with or without polydactyly retinitis pigmentosa 71 Bardet-Biedl syndrome 20

Similar variants

IFT172 p.Val482Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
IFT172 p.Val482Leu 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-val482ile (accessed [today's date]).

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