Is DYSF p.Ala470Val (c.1409C>T) pathogenic?

DYSF p.Ala470Val (c.1409C>T) is classified Uncertain significance in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-13). AlphaMissense: likely pathogenic (0.6512); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with DYSF p.Ala470Val (c.1409C>T)?

DYSF p.Ala470Val (c.1409C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYSF p.Ala470Val (c.1409C>T) in the general population?

DYSF p.Ala470Val (c.1409C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DYSF p.Ala470Val (c.1409C>T)?

AlphaMissense predicts likely pathogenic (score 0.6512) — an in-silico prediction, not a clinical call.

DYSF p.Ala470Val

c.1409C>T · rs1214232857 · VCV2289588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6512 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6512	likely pathogenic
REVEL	0.502	indeterminate
SaProt	LLR -3.01	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 85 kb · p 0.54 · regional, not allelic
Overall
CADD	24.9	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 A438V vs ClinVar A470V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,028 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,886 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.Ala470Val
Coding: c.1409C>T
MANE Select: NM_001130987
dbSNP: rs1214232857
Type: single nucleotide variant
Location: chr2:71535049 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 470: a β-strand; the c2 3 domain

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

Similar variants

DYSF p.Ala1024Pro Uncertain significance ★★ ⚠ same condition
DYSF p.Ala736Thr Uncertain significance ★★ ⚠ same condition
DYSF p.Ala829Val Uncertain significance ★★ ⚠ same condition
DYSF p.Arg1062His Uncertain significance ★★ ⚠ same condition
DYSF p.Arg1102Leu Uncertain significance ★★ ⚠ same condition
DYSF p.Arg1111Cys Uncertain significance ★★ ⚠ same condition
DYSF p.Arg1169His Uncertain significance ★★ ⚠ same condition
DYSF p.Arg1431His Uncertain significance ★★ ⚠ 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-ala470val (accessed [today's date]).

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