Is ACSS2 p.Gly608Val (c.1823G>T) pathogenic?

ACSS2 p.Gly608Val (c.1823G>T) is classified Uncertain significance in ACSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely pathogenic (0.977); Very rare (popmax 0.00339%, nfe).

How common is ACSS2 p.Gly608Val (c.1823G>T) in the general population?

ACSS2 p.Gly608Val (c.1823G>T) is very rare (popmax 0.00339%, nfe) (gnomAD).

What do computational predictors say about ACSS2 p.Gly608Val (c.1823G>T)?

AlphaMissense predicts likely pathogenic (score 0.977) — an in-silico prediction, not a clinical call.

ACSS2 p.Gly608Val

c.1823G>T · VCV4637064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.977	likely pathogenic · top 8% in ACSS2
REVEL	0.753	pathogenic-leaning
SaProt	LLR -11.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 51 kb · p 4e-07 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00339% European (non-Finnish) · 40/1,180,030 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00301% 44/1,461,884 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00339%	29,501
Remaining individualsnot grpmax-eligible	0.0032%	31,255
African / African-American	0.00133%	75,054
South Asian	0.0011%	91,090

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: ACSS2
Protein: p.Gly608Val
Coding: c.1823G>T
MANE Select: NM_018677
Type: single nucleotide variant
Location: chr20:34926201 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.14

Full ACSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSS2 p.Gly608Ser Uncertain significance ★ ⚠ same residue
ACSS2 p.Cys300Ser Benign ★★ ⚠ same type
ACSS2 p.Pro42Thr Benign ★★ same type
ACSS2 c.834+791A>T Uncertain significance ★ same type
ACSS2 c.834+805C>T Uncertain significance ★ same type
ACSS2 c.834+806G>A Uncertain significance ★ same type
ACSS2 p.Ala181Val Uncertain significance ★ ⚠ same type
ACSS2 p.Ala233Asp 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/acss2-p-gly608val (accessed [today's date]).

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