Is ACCSL p.Arg4Gln (c.11G>A) pathogenic?

ACCSL p.Arg4Gln (c.11G>A) is classified Uncertain significance in ACCSL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely benign (0.0733); Ultra-rare (popmax 0.0165%, mid).

How common is ACCSL p.Arg4Gln (c.11G>A) in the general population?

ACCSL p.Arg4Gln (c.11G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ACCSL p.Arg4Gln (c.11G>A)?

AlphaMissense predicts likely benign (score 0.0733) — an in-silico prediction, not a clinical call.

ACCSL p.Arg4Gln

c.11G>A · rs370567159 · VCV3136128

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0733	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.74	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 -5.3	GERP -3.1
Regional constraint	o/e 0.91	unconstrained · MANE · 12 kb · p 0.012 · regional, not allelic
Overall
CADD	0.001	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

Grpmax group 0.0165% Middle Eastern · 1/6,064 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00249% 40/1,608,306 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,064
South Asian	0.00549%	18,204
European (non-Finnish)	0.00281%	35,614
African / African-American	0.00134%	74,818

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: ACCSL
Protein: p.Arg4Gln
Coding: c.11G>A
MANE Select: NM_001031854
dbSNP: rs370567159
Type: single nucleotide variant
Location: chr11:44048047 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.52
Residue 4: the 'disordered' region

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

Similar variants

ACCSL p.Ala111Val Uncertain significance ★ ⚠ same type
ACCSL p.Ala248Val Uncertain significance ★ ⚠ same type
ACCSL p.Ala460Val Uncertain significance ★ ⚠ same type
ACCSL p.Ala87Val Uncertain significance ★ ⚠ same type
ACCSL p.Arg102Ser Uncertain significance ★ ⚠ same type
ACCSL p.Arg133His Uncertain significance ★ ⚠ same type
ACCSL p.Arg138Cys Uncertain significance ★ ⚠ same type
ACCSL p.Arg214Gln 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/accsl-p-arg4gln (accessed [today's date]).

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