Is ACSS3 p.His195Asn (c.583C>A) pathogenic?

ACSS3 p.His195Asn (c.583C>A) is classified Uncertain significance in ACSS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely pathogenic (0.9206); Absent from gnomAD v4.1.

How common is ACSS3 p.His195Asn (c.583C>A) in the general population?

ACSS3 p.His195Asn (c.583C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSS3 p.His195Asn (c.583C>A)?

AlphaMissense predicts likely pathogenic (score 0.9206) — an in-silico prediction, not a clinical call.

ACSS3 p.His195Asn

c.583C>A · VCV4637085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9206 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,260)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9206	likely pathogenic
REVEL	0.666	pathogenic-leaning
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 177 kb · p 0.074 · regional, not allelic
Overall
CADD	28.4	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

No allele count reported in gnomAD v4.1 (AN 1,606,260). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACSS3
Protein: p.His195Asn
Coding: c.583C>A
MANE Select: NM_024560
Type: single nucleotide variant
Location: chr12:81134942 (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-his195asn (accessed [today's date]).

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