Is ACCSL p.Thr41Met (c.122C>T) pathogenic?

ACCSL p.Thr41Met (c.122C>T) is classified Uncertain significance in ACCSL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.0748); Ultra-rare (popmax 0.0799%, afr).

How common is ACCSL p.Thr41Met (c.122C>T) in the general population?

ACCSL p.Thr41Met (c.122C>T) is ultra-rare (popmax 0.0799%, afr) (gnomAD).

What do computational predictors say about ACCSL p.Thr41Met (c.122C>T)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

ACCSL p.Thr41Met

c.122C>T · rs374220502 · VCV2510225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0799%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.70	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 0.16	GERP -3.1
Regional constraint	o/e 0.91	unconstrained · MANE · 12 kb · p 0.012 · regional, not allelic
Overall
CADD	2.067	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 0.0799% African / African-American · 60/75,050 alleles

Filtering AF 0.0637% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0579%

Overall 0.0183% 295/1,614,188 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0799%	1,251
Remaining individualsnot grpmax-eligible	0.0256%	3,907
European (non-Finnish)	0.0173%	5,785
Admixed American	0.0167%	6,003
South Asian	0.00329%	30,363
Finnishnot grpmax-eligible	0.00312%	32,005

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.Thr41Met
Coding: c.122C>T
MANE Select: NM_001031854
dbSNP: rs374220502
Type: single nucleotide variant
Location: chr11:44048158 (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-thr41met (accessed [today's date]).

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