Is UACA p.Ala255Pro (c.763G>C) pathogenic?

UACA p.Ala255Pro (c.763G>C) is classified Uncertain significance in UACA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely pathogenic (0.7944); Very rare (popmax 0.00212%, nfe).

How common is UACA p.Ala255Pro (c.763G>C) in the general population?

UACA p.Ala255Pro (c.763G>C) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about UACA p.Ala255Pro (c.763G>C)?

AlphaMissense predicts likely pathogenic (score 0.7944) — an in-silico prediction, not a clinical call.

UACA p.Ala255Pro

c.763G>C · rs1470949991 · VCV2471786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7944	likely pathogenic · top 8% in UACA
REVEL	0.184	benign-leaning
SaProt	LLR -17.91	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 106 kb · p 0.31 · regional, not allelic
Overall
CADD	24.5	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 0.00212% European (non-Finnish) · 25/1,178,228 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00168% 27/1,608,464 alleles · very rare exomes 24/1,456,306 · genomes 3/152,158 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,129
Remaining individualsnot grpmax-eligible	0.00161%	62,272
African / African-American	0.00134%	74,564

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.Ala255Pro
Coding: c.763G>C
MANE Select: NM_018003
dbSNP: rs1470949991
Type: single nucleotide variant
Location: chr15:70684286 (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.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
UACA p.Ala203Gly 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-ala255pro (accessed [today's date]).

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