Is ACD p.Gly63Ala (c.188G>C) pathogenic?

ACD p.Gly63Ala (c.188G>C) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). AlphaMissense: likely pathogenic (0.7133); Absent from gnomAD v4.1; Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Gly63Ala (c.188G>C)?

ACD p.Gly63Ala (c.188G>C) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Gly63Ala (c.188G>C) in the general population?

ACD p.Gly63Ala (c.188G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACD p.Gly63Ala (c.188G>C)?

AlphaMissense predicts likely pathogenic (score 0.7133) — an in-silico prediction, not a clinical call.

ACD p.Gly63Ala

c.188G>C · rs2543610267 · VCV2170776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7133 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
AlphaMissense	0.7133	likely pathogenic · top 9% in ACD
REVEL	0.297	indeterminate
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	26.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACD
Protein: p.Gly63Ala
Coding: c.188G>C
MANE Select: NM_001082486
dbSNP: rs2543610267
Type: single nucleotide variant
Location: chr16:67659957 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB

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

Disease context

dyskeratosis congenita, autosomal dominant 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACD p.Gly63= Likely benign ★ same residue
ACD p.Gly63Arg Uncertain significance ★ ⚠ same residue
ACD p.Pro63Ala Uncertain significance ★ same residue
ACD p.Pro63= Likely benign ★ same residue
ACD c.645+2T>C Uncertain significance ★★ same condition
ACD c.99+5G>A Uncertain significance ★★ same condition
ACD c.-20C>T Uncertain significance ★★ same condition
ACD c.-24C>T 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-gly63ala (accessed [today's date]).

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