Is UACA p.Glu867= (c.2601G>A) pathogenic?

UACA p.Glu867= (c.2601G>A) is classified Benign in UACA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-30). Common (popmax 5.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with UACA-related disorder.

What condition is associated with UACA p.Glu867= (c.2601G>A)?

UACA p.Glu867= (c.2601G>A) is associated with UACA-related disorder (ClinVar).

UACA p.Glu867=

Q: How common is UACA p.Glu867= (c.2601G>A) in the general population?

UACA p.Glu867= (c.2601G>A) is common (popmax 5.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2601G>A · rs61742861 · VCV3056943

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.6%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.097	GERP 0.42
Overall
CADD	0.963	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.6% African / African-American · 4,193/74,900 alleles

Filtering AF 5.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4%

Overall 0.295% 4,763/1,613,292 alleles · common exomes 2,387/1,461,244 · genomes 2,376/152,048 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.6%	18
Remaining individualsnot grpmax-eligible	0.333%	300
Admixed American	0.254%	394
Middle Eastern	0.132%	757
South Asian	0.123%	813
European (non-Finnish)	0.00763%	13,110

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.Glu867=
Coding: c.2601G>A
MANE Select: NM_018003
dbSNP: rs61742861
Type: single nucleotide variant
Location: chr15:70668083 (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-glu867 (accessed [today's date]).

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