Is AHNAK p.Ala137= (c.411C>T) pathogenic?

AHNAK p.Ala137= (c.411C>T) is classified Likely benign in AHNAK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-08). Ultra-rare (popmax 0.0227%, afr); Associated with AHNAK-related disorder.

What condition is associated with AHNAK p.Ala137= (c.411C>T)?

AHNAK p.Ala137= (c.411C>T) is associated with AHNAK-related disorder (ClinVar).

How common is AHNAK p.Ala137= (c.411C>T) in the general population?

AHNAK p.Ala137= (c.411C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

AHNAK p.Ala137=

c.411C>T · rs199527649 · VCV3035839

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Conditions

AHNAK-related disorder

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 -0.1	GERP -0.86
Overall
CADD	9.206	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,868 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00713% 115/1,612,658 alleles · ultra-rare exomes 93/1,460,578 · genomes 22/152,080 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,404
Admixed American	0.01%	9,973
European (non-Finnish)	0.00738%	13,558
Remaining individualsnot grpmax-eligible	0.00641%	15,609
East Asian	0.00223%	44,882

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: AHNAK
Protein: p.Ala137=
Coding: c.411C>T
MANE Select: NM_001620 · reported on NM_024060
dbSNP: rs199527649
Type: single nucleotide variant
Location: chr11:62491763 (GRCh38)
Gene constraint: LOEUF 0.793 · pLI <0.01 (gnomAD)

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

Disease context

AHNAK-related disorder

Similar variants

AHNAK p.Phe934Leu Uncertain significance ★ same condition
AHNAK p.Asp5419Asn Uncertain significance ⚠ same condition
AHNAK p.Glu4626Lys Likely benign same condition
AHNAK p.Gly138= Likely benign same condition
AHNAK p.Gly148Val Benign same condition
AHNAK p.Leu122Val Benign same condition
AHNAK p.Val142Ile Likely benign same condition
AHNAK p.Glu5_Thr6insGlu Benign 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/ahnak-p-ala137 (accessed [today's date]).

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