Is ACY3 p.Arg32Trp (c.94C>T) pathogenic?

ACY3 p.Arg32Trp (c.94C>T) is classified Uncertain significance in ACY3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: likely benign (0.1471); Very rare (popmax 0.00478%, nfe).

How common is ACY3 p.Arg32Trp (c.94C>T) in the general population?

ACY3 p.Arg32Trp (c.94C>T) is very rare (popmax 0.00478%, nfe) (gnomAD).

What do computational predictors say about ACY3 p.Arg32Trp (c.94C>T)?

AlphaMissense predicts likely benign (score 0.1471) — an in-silico prediction, not a clinical call.

ACY3 p.Arg32Trp

c.94C>T · rs779671699 · VCV2214427

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1471 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00478%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1471	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -12.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.18	GERP -2.7
Regional constraint	o/e 0.99	unconstrained · MANE · 4,316 bp · p 0.86 · regional, not allelic
Overall
CADD	21.4	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 0.00478% European (non-Finnish) · 56/1,170,336 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0034%

Overall 0.00389% 62/1,594,520 alleles · very rare exomes 57/1,442,290 · genomes 5/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00478%	20,899
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,212
African / African-American	0.00268%	37,312
Admixed American	0.00175%	57,258
Remaining individualsnot grpmax-eligible	0.00162%	61,672
South Asian	0.00113%	88,888

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: ACY3
Protein: p.Arg32Trp
Coding: c.94C>T
MANE Select: NM_080658
dbSNP: rs779671699
Type: single nucleotide variant
Location: chr11:67646950 (GRCh38)
Gene constraint: LOEUF 1.196 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.61
Residue 32: the 'hydrolytic domain' region

Full ACY3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACY3 p.Arg32Gln Uncertain significance ★ ⚠ same residue
ACY3 p.Arg32Gly Uncertain significance ★ ⚠ same residue
ACY3 p.Ala120Gly Uncertain significance ★ ⚠ same type
ACY3 p.Ala128Thr Uncertain significance ★ ⚠ same type
ACY3 p.Ala15Ser Uncertain significance ★ ⚠ same type
ACY3 p.Ala222Asp Uncertain significance ★ ⚠ same type
ACY3 p.Ala294Asp Uncertain significance ★ ⚠ same type
ACY3 p.Ala310Ser Uncertain significance ★ ⚠ same type

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/acy3-p-arg32trp (accessed [today's date]).

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