Is UACA p.Tyr985= (c.2955C>T) pathogenic?

UACA p.Tyr985= (c.2955C>T) is classified Benign in UACA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 79%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with UACA-related disorder.

What condition is associated with UACA p.Tyr985= (c.2955C>T)?

UACA p.Tyr985= (c.2955C>T) is associated with UACA-related disorder (ClinVar).

UACA p.Tyr985=

Q: How common is UACA p.Tyr985= (c.2955C>T) in the general population?

UACA p.Tyr985= (c.2955C>T) is common (popmax 79%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2955C>T · rs934005 · VCV3059570

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 79%, nfe) — 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 -2.2	GERP -4.4
Overall
CADD	0.388	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 79% European (non-Finnish) · 932,412/1,179,940 alleles

Filtering AF 78.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 78.8%

Overall 74.8% 1,206,589/1,613,738 alleles · common exomes 1,108,663/1,461,724 · genomes 97,926/152,014 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	83.4%	1
European (non-Finnish)grpmax	79%	1
Admixed American	76%	1
Middle Eastern	75.6%	1
Ashkenazi Jewishnot grpmax-eligible	75.1%	1
Remaining individualsnot grpmax-eligible	73.2%	1
Finnishnot grpmax-eligible	71.3%	1
South Asian	66.1%	2
East Asian	52.1%	2
African / African-American	34.9%	3

Amish 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.Tyr985=
Coding: c.2955C>T
MANE Select: NM_018003
dbSNP: rs934005
Type: single nucleotide variant
Location: chr15:70667729 (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-tyr985 (accessed [today's date]).

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