Is UACA p.Leu426Pro (c.1277T>C) pathogenic?

UACA p.Leu426Pro (c.1277T>C) is classified Uncertain significance in UACA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-19). AlphaMissense: ambiguous (0.4422); Absent from gnomAD v4.1.

How common is UACA p.Leu426Pro (c.1277T>C) in the general population?

UACA p.Leu426Pro (c.1277T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UACA p.Leu426Pro (c.1277T>C)?

AlphaMissense predicts ambiguous (score 0.4422) — an in-silico prediction, not a clinical call.

UACA p.Leu426Pro

c.1277T>C · rs2505340163 · VCV2272225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4422 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4422	ambiguous
REVEL	0.386	indeterminate
SaProt	LLR -6.04	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UACA
Protein: p.Leu426Pro
Coding: c.1277T>C
MANE Select: NM_018003
dbSNP: rs2505340163
Type: single nucleotide variant
Location: chr15:70669407 (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-leu426pro (accessed [today's date]).

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