Is DYSF p.Pro144Gln (c.431C>A) pathogenic?

DYSF p.Pro144Gln (c.431C>A) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0806); Rare (popmax 0.131%, afr); Associated with Inborn genetic diseases.

How common is DYSF p.Pro144Gln (c.431C>A) in the general population?

DYSF p.Pro144Gln (c.431C>A) is rare (popmax 0.131%, afr) (gnomAD).

What do computational predictors say about DYSF p.Pro144Gln (c.431C>A)?

AlphaMissense predicts likely benign (score 0.0806) — an in-silico prediction, not a clinical call.

DYSF p.Pro144Gln

Q: What condition is associated with DYSF p.Pro144Gln (c.431C>A)?

DYSF p.Pro144Gln (c.431C>A) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2B, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.431C>A · rs139654844 · VCV94322

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0806 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.131%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -7.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.68, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 85 kb · p 0.54 · regional, not allelic
Overall
CADD	22.0	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 P143Q vs ClinVar P144Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% African / African-American · 96/73,174 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00677% 105/1,551,282 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.131%	762
Admixed American	0.0098%	10,202
Remaining individualsnot grpmax-eligible	0.00499%	20,035
European (non-Finnish)	8.72e-05%	1,146,753

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.Pro144Gln
Coding: c.431C>A
MANE Select: NM_001130987
dbSNP: rs139654844
Type: single nucleotide variant
Location: chr2:71511892 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 144: the 'disordered' region

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: autosomal recessive limb-girdle muscular dystrophy type 2B neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Similar variants

DYSF p.Pro144Leu Uncertain significance ★★ ⚠ same residue
DYSF p.Pro144= Likely benign ★ 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+1G>C Pathogenic ★★★ same condition
DYSF c.1149+4A>G 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-pro144gln (accessed [today's date]).

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