Is DMD p.Asn135Ser (c.404A>G) pathogenic?

DMD p.Asn135Ser (c.404A>G) is classified Likely benign in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-11). AlphaMissense: likely benign (0.1362); Ultra-rare (popmax 0.0122%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Asn135Ser (c.404A>G)?

DMD p.Asn135Ser (c.404A>G) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Asn135Ser (c.404A>G) in the general population?

DMD p.Asn135Ser (c.404A>G) is ultra-rare (popmax 0.0122%, afr) (gnomAD).

What do computational predictors say about DMD p.Asn135Ser (c.404A>G)?

AlphaMissense predicts likely benign (score 0.1362) — an in-silico prediction, not a clinical call.

DMD p.Asn135Ser

c.404A>G · rs764808552 · VCV1189170

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1362 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1362	likely benign
REVEL	0.19	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	23.2	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 0.0122% African / African-American · 7/57,259 alleles

Filtering AF 0.00566% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00405%

Overall 0.000826% 10/1,210,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0122%	8,180
Admixed American	0.00437%	22,859
Remaining individualsnot grpmax-eligible	0.0021%	47,592

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: DMD
Protein: p.Asn135Ser
Coding: c.404A>G
MANE Select: NM_004006
dbSNP: rs764808552
Type: single nucleotide variant
Location: chrX:32816594 (GRCh38)
Residue 135: the calponin-homology (ch) 2 domain; the 'actin-binding' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Asn135= Likely benign ★★ same residue
DMD p.Asn135Thr Uncertain significance ★ same residue
DMD p.Asn135fs Pathogenic ★ same residue
DMD c.10086+1G>A Pathogenic ★★ same condition
DMD c.10086+1G>T Pathogenic ★★ same condition
DMD c.10086+2T>C Pathogenic ★★ same condition
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.10223+1G>A Pathogenic ★★ 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/dmd-p-asn135ser (accessed [today's date]).

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