Is UACA p.His928= (c.2784C>T) pathogenic?

UACA p.His928= (c.2784C>T) is classified Likely benign in UACA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Rare (popmax 0.227%, nfe); Associated with UACA-related disorder.

What condition is associated with UACA p.His928= (c.2784C>T)?

UACA p.His928= (c.2784C>T) is associated with UACA-related disorder (ClinVar).

How common is UACA p.His928= (c.2784C>T) in the general population?

UACA p.His928= (c.2784C>T) is rare (popmax 0.227%, nfe) (gnomAD).

UACA p.His928=

c.2784C>T · rs138757062 · VCV3033276

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.227%, nfe)

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 -3.3	GERP -4.4
Overall
CADD	0.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.227% European (non-Finnish) · 2,673/1,179,974 alleles

Filtering AF 0.219% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.216%

Overall 0.19% 3,067/1,613,890 alleles · rare exomes 2,842/1,461,756 · genomes 225/152,134 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.258%	388
European (non-Finnish)grpmax	0.227%	441
Admixed American	0.209%	480
Finnishnot grpmax-eligible	0.0844%	1,185
African / African-American	0.044%	2,273
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
South Asian	0.0132%	7,588
East Asian	0.00223%	44,868

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His928=
Coding: c.2784C>T
MANE Select: NM_018003
dbSNP: rs138757062
Type: single nucleotide variant
Location: chr15:70667900 (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-his928 (accessed [today's date]).

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