Is ACCSL p.Thr200Ile (c.599C>T) pathogenic?

ACCSL p.Thr200Ile (c.599C>T) is classified Uncertain significance in ACCSL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: likely benign (0.0798); Ultra-rare (popmax 0.0253%, sas).

How common is ACCSL p.Thr200Ile (c.599C>T) in the general population?

ACCSL p.Thr200Ile (c.599C>T) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about ACCSL p.Thr200Ile (c.599C>T)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

ACCSL p.Thr200Ile

c.599C>T · rs375824761 · VCV3136193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -7.88	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 -7.8	GERP -3.7
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 0.0253% South Asian · 23/91,076 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00564% 91/1,614,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
European (non-Finnish)	0.00551%	18,154
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00134%	74,902

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.Thr200Ile
Coding: c.599C>T
MANE Select: NM_001031854
dbSNP: rs375824761
Type: single nucleotide variant
Location: chr11:44050586 (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-thr200ile (accessed [today's date]).

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