Is UACA p.Asn325Ser (c.974A>G) pathogenic?

UACA p.Asn325Ser (c.974A>G) is classified Benign in UACA (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-04-04). AlphaMissense: likely benign (0.0783); Common (popmax 5.94%, afr) — too common for a highly-penetrant pathogenic allele; Associated with UACA-related disorder.

What condition is associated with UACA p.Asn325Ser (c.974A>G)?

UACA p.Asn325Ser (c.974A>G) is associated with UACA-related disorder (ClinVar).

What do computational predictors say about UACA p.Asn325Ser (c.974A>G)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

UACA p.Asn325Ser

Q: How common is UACA p.Asn325Ser (c.974A>G) in the general population?

UACA p.Asn325Ser (c.974A>G) is common (popmax 5.94%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.974A>G · rs61746365 · VCV3038728

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.94%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

UACA-related disorder

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.13	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 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 106 kb · p 0.31 · regional, not allelic
Overall
CADD	17.87	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 5.94% African / African-American · 4,434/74,660 alleles

Filtering AF 5.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.73%

Overall 0.361% 5,802/1,607,466 alleles · common exomes 3,188/1,455,170 · genomes 2,614/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.94%	17
Admixed American	0.672%	149
Remaining individualsnot grpmax-eligible	0.557%	179
Middle Eastern	0.266%	376
South Asian	0.0512%	1,952
European (non-Finnish)	0.0471%	2,123
Finnishnot grpmax-eligible	0.0111%	8,969
East Asian	0.00448%	22,336
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,452

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.Asn325Ser
Coding: c.974A>G
MANE Select: NM_018003
dbSNP: rs61746365
Type: single nucleotide variant
Location: chr15:70678124 (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.Asn371= 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-asn325ser (accessed [today's date]).

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