Is ACCS p.Arg384Trp (c.1150C>T) pathogenic?

ACCS p.Arg384Trp (c.1150C>T) is classified Uncertain significance in ACCS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: ambiguous (0.3924); Ultra-rare (popmax 0.0173%, afr).

How common is ACCS p.Arg384Trp (c.1150C>T) in the general population?

ACCS p.Arg384Trp (c.1150C>T) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about ACCS p.Arg384Trp (c.1150C>T)?

AlphaMissense predicts ambiguous (score 0.3924) — an in-silico prediction, not a clinical call.

ACCS p.Arg384Trp

c.1150C>T · VCV3476775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3924 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3924	ambiguous
REVEL	0.822	moderately pathogenic-leaning
SaProt	LLR -13.12	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.26 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% African / African-American · 13/75,036 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.0031% 50/1,614,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,772
South Asian	0.00439%	22,772
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.00254%	39,334
Admixed American	0.00167%	60,024

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: ACCS
Protein: p.Arg384Trp
Coding: c.1150C>T
MANE Select: NM_032592
Type: single nucleotide variant
Location: chr11:44083207 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63

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

Similar variants

ACCS p.Arg384Gln Uncertain significance ★ ⚠ same residue
ACCS p.Arg489Cys Benign ★★ same type
ACCS p.Val202= Benign ★★ same type
ACCS p.Ala11Val Uncertain significance ★ ⚠ same type
ACCS p.Ala237Thr Uncertain significance ★ ⚠ same type
ACCS p.Ala77Ser Uncertain significance ★ ⚠ same type
ACCS p.Arg124Lys Uncertain significance ★ ⚠ same type
ACCS p.Arg142Gln 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/accs-p-arg384trp (accessed [today's date]).

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