Is ACD p.Leu97Pro (c.290T>C) pathogenic?

ACD p.Leu97Pro (c.290T>C) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-29). AlphaMissense: likely pathogenic (0.927); Absent from gnomAD v4.1; Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Leu97Pro (c.290T>C)?

ACD p.Leu97Pro (c.290T>C) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Leu97Pro (c.290T>C) in the general population?

ACD p.Leu97Pro (c.290T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACD p.Leu97Pro (c.290T>C)?

AlphaMissense predicts likely pathogenic (score 0.927) — an in-silico prediction, not a clinical call.

ACD p.Leu97Pro

c.290T>C · rs2543609097 · VCV1959456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.927 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,954)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
AlphaMissense	0.927	likely pathogenic · top 3% in ACD
REVEL	0.385	indeterminate
SaProt	LLR -14.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,612,954). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACD
Protein: p.Leu97Pro
Coding: c.290T>C
MANE Select: NM_001082486
dbSNP: rs2543609097
Type: single nucleotide variant
Location: chr16:67659748 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 97: a β-strand

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.Leu97= Likely benign ★★ same residue
ACD p.Leu97Val Uncertain significance ★ ⚠ 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
ACD c.-26T>G Uncertain significance ★★ same condition
ACD c.-29C>A 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-leu97pro (accessed [today's date]).

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