Is UACA p.Val1223= (c.3669A>G) pathogenic?

UACA p.Val1223= (c.3669A>G) is classified Likely benign in UACA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Rare (popmax 0.493%, afr); Associated with UACA-related disorder.

What condition is associated with UACA p.Val1223= (c.3669A>G)?

UACA p.Val1223= (c.3669A>G) is associated with UACA-related disorder (ClinVar).

How common is UACA p.Val1223= (c.3669A>G) in the general population?

UACA p.Val1223= (c.3669A>G) is rare (popmax 0.493%, afr) (gnomAD).

UACA p.Val1223=

c.3669A>G · rs147338503 · VCV3040009

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.493%, afr)

Conditions

UACA-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -3.9
Overall
CADD	0.247	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.493% African / African-American · 370/75,014 alleles

Filtering AF 0.452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.435%

Overall 0.0291% 469/1,613,470 alleles · rare exomes 197/1,461,142 · genomes 272/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.493%	203
Admixed American	0.112%	895
Middle Eastern	0.0496%	2,017
Remaining individualsnot grpmax-eligible	0.0336%	2,976
South Asian	0.0044%	22,742
European (non-Finnish)	0.000339%	294,977

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.Val1223=
Coding: c.3669A>G
MANE Select: NM_018003
dbSNP: rs147338503
Type: single nucleotide variant
Location: chr15:70667015 (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-val1223 (accessed [today's date]).

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