Is ACSS1 p.Ser44Arg (c.132C>A) pathogenic?

ACSS1 p.Ser44Arg (c.132C>A) is classified Uncertain significance in ACSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.1257); Absent from gnomAD v4.1.

How common is ACSS1 p.Ser44Arg (c.132C>A) in the general population?

ACSS1 p.Ser44Arg (c.132C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSS1 p.Ser44Arg (c.132C>A)?

AlphaMissense predicts likely benign (score 0.1257) — an in-silico prediction, not a clinical call.

ACSS1 p.Ser44Arg

c.132C>A · rs2515025471 · VCV3140842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1257 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,574,942)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1257	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.14	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 2.7	GERP 0.088, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.75 · regional, not allelic
Overall
CADD	14.96	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,574,942). 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: ACSS1
Protein: p.Ser44Arg
Coding: c.132C>A
MANE Select: NM_032501
dbSNP: rs2515025471
Type: single nucleotide variant
Location: chr20:25057971 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.07 · 9 PDB
Residue 44: the 'disordered' region

Full ACSS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSS1 p.Val479Ile Benign ★★ ⚠ same type
ACSS1 p.Ala181Gly Uncertain significance ★ ⚠ same type
ACSS1 p.Ala211Val Uncertain significance ★ ⚠ same type
ACSS1 p.Ala279Thr Uncertain significance ★ ⚠ same type
ACSS1 p.Ala316Thr Uncertain significance ★ ⚠ same type
ACSS1 p.Ala37Glu Uncertain significance ★ ⚠ same type
ACSS1 p.Ala454Thr Uncertain significance ★ ⚠ same type
ACSS1 p.Ala602Val 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/acss1-p-ser44arg (accessed [today's date]).

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