Is UACA p.Met403Val (c.1207A>G) pathogenic?

UACA p.Met403Val (c.1207A>G) is classified Benign in UACA (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-04-18). AlphaMissense: likely benign (0.0523); Low-frequency (popmax 1.51%, sas); Associated with UACA-related disorder.

What condition is associated with UACA p.Met403Val (c.1207A>G)?

UACA p.Met403Val (c.1207A>G) is associated with UACA-related disorder (ClinVar).

How common is UACA p.Met403Val (c.1207A>G) in the general population?

UACA p.Met403Val (c.1207A>G) is low-frequency (popmax 1.51%, sas) (gnomAD).

What do computational predictors say about UACA p.Met403Val (c.1207A>G)?

AlphaMissense predicts likely benign (score 0.0523) — an in-silico prediction, not a clinical call.

UACA p.Met403Val

c.1207A>G · rs150049035 · VCV3056303

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0523 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.51%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

UACA-related disorder

Computational evidence

Protein change
AlphaMissense	0.0523	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.21	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 0.11	GERP -4.3, phastCons 0.61
Regional constraint	o/e 0.97	unconstrained · MANE · 106 kb · p 0.31 · regional, not allelic
Overall
CADD	1.018	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 1.51% South Asian · 1,273/84,496 alleles

Filtering AF 1.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.41%

Overall 0.395% 6,236/1,577,888 alleles · low-frequency exomes 5,684/1,425,694 · genomes 552/152,194 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.51%	66
Middle Eastern	1.19%	84
Ashkenazi Jewishnot grpmax-eligible	1.03%	97
Remaining individualsnot grpmax-eligible	0.515%	194
Amishnot grpmax-eligible	0.439%	228
Admixed American	0.432%	231
European (non-Finnish)	0.334%	299
Finnishnot grpmax-eligible	0.189%	529
African / African-American	0.0642%	1,558
East Asian	0.00678%	14,753

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.Met403Val
Coding: c.1207A>G
MANE Select: NM_018003
dbSNP: rs150049035
Type: single nucleotide variant
Location: chr15:70671053 (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

Disease context

UACA-related disorder

Similar variants

UACA c.79-6T>C Benign same condition
UACA c.822+5A>G Benign same condition
UACA c.999+9A>G Likely benign same condition
UACA p.Ala108= Likely benign same condition
UACA p.Ala621= Likely benign same condition
UACA p.Asn1336= Benign same condition
UACA p.Asn1336Ser Likely benign same condition
UACA p.Asn325Ser Benign 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/uaca-p-met403val (accessed [today's date]).

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