Is ACCS p.Cys20Arg (c.58T>C) pathogenic?

ACCS p.Cys20Arg (c.58T>C) is classified Uncertain significance in ACCS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-08). AlphaMissense: likely benign (0.073); Ultra-rare (popmax 0.0117%, nfe).

How common is ACCS p.Cys20Arg (c.58T>C) in the general population?

ACCS p.Cys20Arg (c.58T>C) is ultra-rare (popmax 0.0117%, nfe) (gnomAD).

What do computational predictors say about ACCS p.Cys20Arg (c.58T>C)?

AlphaMissense predicts likely benign (score 0.073) — an in-silico prediction, not a clinical call.

ACCS p.Cys20Arg

c.58T>C · rs141016787 · VCV2409644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.073 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.073	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -5.16	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 0.23	GERP -1.1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.26 · regional, not allelic
Overall
CADD	13.53	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 0.0117% European (non-Finnish) · 138/1,180,008 alleles

Filtering AF 0.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00948%

Overall 0.00861% 139/1,614,158 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0117%	8,551
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Cys20Arg
Coding: c.58T>C
MANE Select: NM_032592
dbSNP: rs141016787
Type: single nucleotide variant
Location: chr11:44067685 (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.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
ACCS p.Arg142Trp 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-cys20arg (accessed [today's date]).

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