Is UACA p.Ala621= (c.1863G>A) pathogenic?

UACA p.Ala621= (c.1863G>A) is classified Likely benign in UACA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-27). Rare (popmax 0.163%, amr); Associated with UACA-related disorder.

What condition is associated with UACA p.Ala621= (c.1863G>A)?

UACA p.Ala621= (c.1863G>A) is associated with UACA-related disorder (ClinVar).

How common is UACA p.Ala621= (c.1863G>A) in the general population?

UACA p.Ala621= (c.1863G>A) is rare (popmax 0.163%, amr) (gnomAD).

UACA p.Ala621=

c.1863G>A · rs189747910 · VCV3048604

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.163%, amr)

Conditions

UACA-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.7	GERP -3.9
Overall
CADD	2.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% Admixed American · 98/59,998 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.00626% 101/1,613,880 alleles · rare exomes 91/1,461,580 · genomes 10/152,300 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.163%	612
Remaining individualsnot grpmax-eligible	0.0016%	62,502
South Asian	0.0011%	91,078
European (non-Finnish)	8.47e-05%	1,180,008

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.Ala621=
Coding: c.1863G>A
MANE Select: NM_018003
dbSNP: rs189747910
Type: single nucleotide variant
Location: chr15:70668821 (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.Asn1336= Benign same condition
UACA p.Asn1336Ser Likely benign same condition
UACA p.Asn325Ser 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-ala621 (accessed [today's date]).

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