Is ACTN2 p.Asp893Val (c.2678A>T) pathogenic?

ACTN2 p.Asp893Val (c.2678A>T) is classified Uncertain significance in ACTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-03). AlphaMissense: likely pathogenic (0.8147); Absent from gnomAD v4.1.

How common is ACTN2 p.Asp893Val (c.2678A>T) in the general population?

ACTN2 p.Asp893Val (c.2678A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTN2 p.Asp893Val (c.2678A>T)?

AlphaMissense predicts likely pathogenic (score 0.8147) — an in-silico prediction, not a clinical call.

ACTN2 p.Asp893Val

c.2678A>T · rs199920384 · VCV1678340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8147 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8147	likely pathogenic
REVEL	0.747	pathogenic-leaning
SaProt	LLR -14.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 25 kb · p 0.0054 · regional, not allelic
Overall
CADD	25.5	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

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: ACTN2
Protein: p.Asp893Val
Coding: c.2678A>T
MANE Select: NM_001103
dbSNP: rs199920384
Type: single nucleotide variant
Location: chr1:236762612 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.88 · 18 PDB

Full ACTN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTN2 p.Asp893Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
ACTN2 p.Asp893Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ACTN2 p.Ala119Thr Pathogenic/Likely pathogenic ★★ same type
ACTN2 p.Leu727Arg Pathogenic/Likely pathogenic ★★ same type
ACTN2 p.Thr247Met Likely pathogenic ★★ same type
ACTN2 c.1107+3G>A Uncertain significance ★★ same type
ACTN2 c.1108-10A>G Uncertain significance ★★ same type
ACTN2 c.1255+1G>C 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/actn2-p-asp893val (accessed [today's date]).

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