Is DMD p.His104Tyr (c.310C>T) pathogenic?

DMD p.His104Tyr (c.310C>T) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-18). AlphaMissense: likely benign (0.3006); Very rare (popmax 0.000671%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.His104Tyr (c.310C>T)?

DMD p.His104Tyr (c.310C>T) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.His104Tyr (c.310C>T) in the general population?

DMD p.His104Tyr (c.310C>T) is very rare (popmax 0.000671%, nfe) (gnomAD).

What do computational predictors say about DMD p.His104Tyr (c.310C>T)?

AlphaMissense predicts likely benign (score 0.3006) — an in-silico prediction, not a clinical call.

DMD p.His104Tyr

c.310C>T · rs757270951 · VCV1727728

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000671%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3006	likely benign
REVEL	0.827	moderately pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	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	26.9	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 0.000671% European (non-Finnish) · 6/893,761 alleles

Filtering AF 0.000241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 6/1,096,058 alleles · very rare

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.His104Tyr
Coding: c.310C>T
MANE Select: NM_004006
dbSNP: rs757270951
Type: single nucleotide variant
Location: chrX:32823342 (GRCh38)
Residue 104: the calponin-homology (ch) 1 domain; an α-helix; 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.His104Leu Likely benign ★ ⚠ 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
DMD c.10223+1G>C Pathogenic ★★ same condition
DMD c.10224-2A>G Likely 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-his104tyr (accessed [today's date]).

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