Is ACTN3 p.Asp36His (c.106G>C) pathogenic?

ACTN3 p.Asp36His (c.106G>C) is classified Likely benign in ACTN3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-10). AlphaMissense: likely pathogenic (0.8312); Low-frequency (popmax 1.15%, eas); Associated with ACTN3-related disorder.

What condition is associated with ACTN3 p.Asp36His (c.106G>C)?

ACTN3 p.Asp36His (c.106G>C) is associated with ACTN3-related disorder (ClinVar).

How common is ACTN3 p.Asp36His (c.106G>C) in the general population?

ACTN3 p.Asp36His (c.106G>C) is low-frequency (popmax 1.15%, eas) (gnomAD).

What do computational predictors say about ACTN3 p.Asp36His (c.106G>C)?

AlphaMissense predicts likely pathogenic (score 0.8312) — an in-silico prediction, not a clinical call.

ACTN3 p.Asp36His

c.106G>C · rs201937354 · VCV3033952

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8312 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Conditions

ACTN3-related disorder

Computational evidence

Protein change
AlphaMissense	0.8312	likely pathogenic
SaProt	LLR -13.32	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 7,650 bp · p 0.64 · regional, not allelic
Overall
CADD	28.7	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 1.15% East Asian · 501/43,650 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.0668% 1,010/1,511,952 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.15%	87
Finnishnot grpmax-eligible	0.46%	217
Remaining individualsnot grpmax-eligible	0.0796%	1,257
South Asian	0.0282%	3,548
European (non-Finnish)	0.0146%	6,860
Admixed American	0.00228%	43,846

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: ACTN3
Protein: p.Asp36His
Coding: c.106G>C
MANE Select: NM_001104
dbSNP: rs201937354
Type: single nucleotide variant
Location: chr11:66547043 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.61 · 3 PDB
Residue 36: the 'actin-binding' region

Full ACTN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ACTN3-related disorder

Similar variants

ACTN3 c.1129-8C>T Likely benign same condition
ACTN3 c.1678-8G>A Benign same condition
ACTN3 p.Ala417Ser Benign same condition
ACTN3 p.Ala469= Likely benign same condition
ACTN3 p.Ala492= Likely benign same condition
ACTN3 p.Ala564= Likely benign same condition
ACTN3 p.Ala881Ser Likely benign ⚠ same condition
ACTN3 p.Arg199Gln Likely benign 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/actn3-p-asp36his (accessed [today's date]).

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