Is DYSF p.Asp1876His (c.5626G>C) pathogenic?

DYSF p.Asp1876His (c.5626G>C) is classified Likely pathogenic in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). AlphaMissense: likely pathogenic (0.9877); Very rare (popmax 0.00169%, amr); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Asp1876His (c.5626G>C) in the general population?

DYSF p.Asp1876His (c.5626G>C) is very rare (popmax 0.00169%, amr) (gnomAD).

What do computational predictors say about DYSF p.Asp1876His (c.5626G>C)?

AlphaMissense predicts likely pathogenic (score 0.9877) — an in-silico prediction, not a clinical call.

DYSF p.Asp1876His

Q: What condition is associated with DYSF p.Asp1876His (c.5626G>C)?

DYSF p.Asp1876His (c.5626G>C) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.5626G>C · rs398123794 · VCV2885593

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9877 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
AlphaMissense	0.9877	likely pathogenic ✓ concordant with ClinVar · top 4% in DYSF
REVEL	0.944	strongly pathogenic-leaning
SaProt	LLR -14.87	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D1837H vs ClinVar D1876H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% Admixed American · 1/59,244 alleles

Overall 0.000657% 1/152,206 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: DYSF
Protein: p.Asp1876His
Coding: c.5626G>C
MANE Select: NM_001130987
dbSNP: rs398123794
Type: single nucleotide variant
Location: chr2:71669191 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1876: the c2 7 domain; a β-strand

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

Disease context

neuromuscular disease caused by qualitative or quantitative defects of dysferlin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYSF p.Asp1876Asn Pathogenic ★★★ same residue
DYSF p.Asp1876Glu Likely pathogenic ★ same residue
DYSF c.1003-3C>A Pathogenic ★★★ same condition
DYSF c.1033+1G>A Pathogenic ★★★ same condition
DYSF c.1033+4A>T Likely pathogenic ★★★ same condition
DYSF c.1149+1G>A Pathogenic ★★★ same condition
DYSF c.1149+4A>G Pathogenic ★★★ same condition
DYSF c.1276+5G>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/dysf-p-asp1876his (accessed [today's date]).

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