Is ACSS3 p.Ile296Val (c.886A>G) pathogenic?

ACSS3 p.Ile296Val (c.886A>G) is classified Likely benign in ACSS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: likely benign (0.0941); Very rare (popmax 0.00669%, eas).

How common is ACSS3 p.Ile296Val (c.886A>G) in the general population?

ACSS3 p.Ile296Val (c.886A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about ACSS3 p.Ile296Val (c.886A>G)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

ACSS3 p.Ile296Val

c.886A>G · VCV3263476

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP -0.18, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 177 kb · p 0.074 · regional, not allelic
Overall
CADD	14.1	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 0.00669% East Asian · 3/44,850 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000248% 4/1,610,742 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,950
European (non-Finnish)	8.49e-05%	1,177,720

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: ACSS3
Protein: p.Ile296Val
Coding: c.886A>G
MANE Select: NM_024560
Type: single nucleotide variant
Location: chr12:81143212 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.93

Full ACSS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSS3 p.Ala193Thr Uncertain significance ★ ⚠ same type
ACSS3 p.Ala262Glu Uncertain significance ★ ⚠ same type
ACSS3 p.Ala317Thr Uncertain significance ★ ⚠ same type
ACSS3 p.Ala377Thr Uncertain significance ★ ⚠ same type
ACSS3 p.Ala53Glu Uncertain significance ★ ⚠ same type
ACSS3 p.Ala570Thr Uncertain significance ★ ⚠ same type
ACSS3 p.Ala657Asp Uncertain significance ★ ⚠ same type
ACSS3 p.Ala80Val 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/acss3-p-ile296val (accessed [today's date]).

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