Is ACCSL p.Trp391Arg (c.1171T>A) pathogenic?

ACCSL p.Trp391Arg (c.1171T>A) is classified Uncertain significance in ACCSL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.8402); Very rare (popmax 0.00833%, amr).

How common is ACCSL p.Trp391Arg (c.1171T>A) in the general population?

ACCSL p.Trp391Arg (c.1171T>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about ACCSL p.Trp391Arg (c.1171T>A)?

AlphaMissense predicts likely pathogenic (score 0.8402) — an in-silico prediction, not a clinical call.

ACCSL p.Trp391Arg

c.1171T>A · VCV4215228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8402 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8402	likely pathogenic · top 1% in ACCSL
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -11.98	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 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 12 kb · p 0.012 · regional, not allelic
Overall
CADD	26.4	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 0.00833% Admixed American · 5/60,030 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.00041% 6/1,461,872 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,006
European (non-Finnish)	8.47e-05%	1,180,043

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.Trp391Arg
Coding: c.1171T>A
MANE Select: NM_001031854
Type: single nucleotide variant
Location: chr11:44056071 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.52

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-trp391arg (accessed [today's date]).

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