Is ANO5 p.Val17Ile (c.49G>A) pathogenic?

ANO5 p.Val17Ile (c.49G>A) is classified Uncertain significance in ANO5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-15). AlphaMissense: likely benign (0.0669); Very rare (popmax 0.000852%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2L.

How common is ANO5 p.Val17Ile (c.49G>A) in the general population?

ANO5 p.Val17Ile (c.49G>A) is very rare (popmax 0.000852%, nfe) (gnomAD).

What do computational predictors say about ANO5 p.Val17Ile (c.49G>A)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

ANO5 p.Val17Ile

Q: What condition is associated with ANO5 p.Val17Ile (c.49G>A)?

ANO5 p.Val17Ile (c.49G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2L, gnathodiaphyseal dysplasia (ClinVar).

Q: How is Anoctamin-5-related limb-girdle muscular dystrophy R12 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.49G>A · rs760992965 · VCV1362404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000852%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2L

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -6.30	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 -4.4	GERP -4.8
Regional constraint	o/e 0.99	unconstrained · MANE · 86 kb · p 0.66 · regional, not allelic
Overall
CADD	0.002	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000852% European (non-Finnish) · 9/1,055,832 alleles

Filtering AF 0.000401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000291%

Overall 0.000612% 9/1,470,614 alleles · very rare exomes 9/1,318,592 · genomes 0/152,022 · joint denominator

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: ANO5
Protein: p.Val17Ile
Coding: c.49G>A
MANE Select: NM_213599
dbSNP: rs760992965
Type: single nucleotide variant
Location: chr11:22203812 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22

Full ANO5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2L — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gnathodiaphyseal dysplasia

For Anoctamin-5-related limb-girdle muscular dystrophy R12 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

ANO5 p.Val17= Likely benign ★ same residue
ANO5 c.1898+1G>A Pathogenic ★★★ same condition
ANO5 c.41-1G>A Pathogenic ★★★ same condition
ANO5 p.Ala432Gly Pathogenic ★★★ ⚠ same condition
ANO5 p.Arg484Cys Likely pathogenic ★★★ same condition
ANO5 p.Arg50Ter Pathogenic ★★★ same condition
ANO5 p.Arg58Trp Pathogenic ★★★ ⚠ same condition
ANO5 p.Arg758Cys 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/ano5-p-val17ile (accessed [today's date]).

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