Is DYSF p.Arg1970His (c.5909G>A) pathogenic?

DYSF p.Arg1970His (c.5909G>A) is classified Likely benign in DYSF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-14). AlphaMissense: likely benign (0.0642); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with DYSF p.Arg1970His (c.5909G>A)?

DYSF p.Arg1970His (c.5909G>A) is associated with Inborn genetic diseases, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

How common is DYSF p.Arg1970His (c.5909G>A) in the general population?

DYSF p.Arg1970His (c.5909G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DYSF p.Arg1970His (c.5909G>A)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

DYSF p.Arg1970His

c.5909G>A · rs1167021157 · VCV2199521

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -4.5
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	6.25	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 R1931H vs ClinVar R1970H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,878 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,613,850 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,439
South Asian	0.0022%	45,538
Admixed American	0.00167%	60,004
European (non-Finnish)	0.000254%	393,304

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.Arg1970His
Coding: c.5909G>A
MANE Select: NM_001130987
dbSNP: rs1167021157
Type: single nucleotide variant
Location: chr2:71679081 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1970: a UniProt-annotated variant site (in lgmdr2); a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Similar variants

DYSF p.Arg1970Cys Conflicting classifications of pathogenicity ★ ⚠ 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
DYSF c.1276+5G>C 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-arg1970his (accessed [today's date]).

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