Is DYSF p.His67= (c.201T>C) pathogenic?

DYSF p.His67= (c.201T>C) is classified Likely benign in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-23). Very rare (popmax 0.00167%, amr); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.His67= (c.201T>C) in the general population?

DYSF p.His67= (c.201T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

DYSF p.His67=

Q: What condition is associated with DYSF p.His67= (c.201T>C)?

DYSF p.His67= (c.201T>C) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.201T>C · rs182555653 · VCV2901083

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.4	GERP -1.8
Overall
CADD	1.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,024 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,132 alleles · very rare exomes 2/1,461,872 · genomes 1/152,260 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,024
European (non-Finnish)	0.000169%	590,009

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.His67=
Coding: c.201T>C
MANE Select: NM_001130987
dbSNP: rs182555653
Type: single nucleotide variant
Location: chr2:71481932 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 67: a β-strand; a UniProt-annotated variant site (in mmd1 and lgmdr2; reduces calcium-sensitive phospholipid binding and interaction with ahnak and ahnak2); the c2 1 domain

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 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
DYSF c.1276+5G>C Pathogenic ★★★ same condition
DYSF c.1481-1G>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/dysf-p-his67 (accessed [today's date]).

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