Is UACA p.Ile182Val (c.544A>G) pathogenic?

UACA p.Ile182Val (c.544A>G) is classified Uncertain significance in UACA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely benign (0.0862); Ultra-rare (popmax 0.0535%, eas).

How common is UACA p.Ile182Val (c.544A>G) in the general population?

UACA p.Ile182Val (c.544A>G) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

What do computational predictors say about UACA p.Ile182Val (c.544A>G)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

UACA p.Ile182Val

c.544A>G · VCV4601052

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -6.06	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 4.3	GERP 0.91, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 106 kb · p 0.31 · regional, not allelic
Overall
CADD	15.33	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0535% East Asian · 24/44,872 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.0039% 63/1,613,976 alleles · ultra-rare exomes 53/1,461,652 · genomes 10/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0535%	1,870
African / African-American	0.0187%	5,360
Remaining individualsnot grpmax-eligible	0.0048%	20,833
European (non-Finnish)	0.0017%	58,993
Admixed American	0.00167%	60,006
South Asian	0.0011%	91,080

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: UACA
Protein: p.Ile182Val
Coding: c.544A>G
MANE Select: NM_018003
Type: single nucleotide variant
Location: chr15:70687598 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.08

Full UACA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UACA p.Ile182Thr Uncertain significance ★ same residue
UACA p.Gln458His Likely benign ★★ same type
UACA c.1222-1G>A Uncertain significance ★ same type
UACA p.Ala1060Ser Uncertain significance ★ ⚠ same type
UACA p.Ala1248Val Uncertain significance ★ ⚠ same type
UACA p.Ala1391Val Uncertain significance ★ ⚠ same type
UACA p.Ala144Val Uncertain significance ★ same type
UACA p.Ala191Val Uncertain significance ★ ⚠ same type

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/uaca-p-ile182val (accessed [today's date]).

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