Is ACD p.Cys187Arg (c.559T>C) pathogenic?

ACD p.Cys187Arg (c.559T>C) is classified Likely benign in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-18). AlphaMissense: likely benign (0.076); Very rare (popmax 0.00161%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Cys187Arg (c.559T>C)?

ACD p.Cys187Arg (c.559T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Cys187Arg (c.559T>C) in the general population?

ACD p.Cys187Arg (c.559T>C) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about ACD p.Cys187Arg (c.559T>C)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

ACD p.Cys187Arg

c.559T>C · rs771799486 · VCV2447154

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -3.44	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 1.6	GERP -0.96, phastCons 0.002
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	2.123	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 0.00161% European (non-Finnish) · 19/1,180,016 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00161% 26/1,613,820 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0094%	10,634
European (non-Finnish)grpmax	0.00161%	62,106
Remaining individualsnot grpmax-eligible	0.0016%	62,476

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACD
Protein: p.Cys187Arg
Coding: c.559T>C
MANE Select: NM_001082486
dbSNP: rs771799486
Type: single nucleotide variant
Location: chr16:67659014 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 187: the 'interaction with pot1' region; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACD p.Cys187Ser Uncertain significance ★ ⚠ same residue
ACD p.Cys187= Likely benign ★ same residue
ACD c.-20C>T Uncertain significance ★★ same condition
ACD c.-26T>G Uncertain significance ★★ same condition
ACD c.-29C>A Uncertain significance ★★ same condition
ACD c.-30C>T Uncertain significance ★★ same condition
ACD c.-35C>T Uncertain significance ★★ same condition
ACD c.-36C>G Uncertain significance ★★ same condition

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/acd-p-cys187arg (accessed [today's date]).

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