Is AHNAK p.Gly343Ser (c.1027G>A) pathogenic?

AHNAK p.Gly343Ser (c.1027G>A) is classified Likely benign in AHNAK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.0815); Ultra-rare (popmax 0.0288%, sas).

How common is AHNAK p.Gly343Ser (c.1027G>A) in the general population?

AHNAK p.Gly343Ser (c.1027G>A) is ultra-rare (popmax 0.0288%, sas) (gnomAD).

What do computational predictors say about AHNAK p.Gly343Ser (c.1027G>A)?

AlphaMissense predicts likely benign (score 0.0815) — an in-silico prediction, not a clinical call.

AHNAK p.Gly343Ser

c.1027G>A · VCV3509385

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0815 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0288%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0815	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.3
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.28 · regional, not allelic
Overall
CADD	6.067	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0288% South Asian · 25/86,710 alleles

Filtering AF 0.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00408% 65/1,594,476 alleles · ultra-rare exomes 61/1,442,256 · genomes 4/152,220 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0288%	3,468
Middle Eastern	0.0167%	5,982
Remaining individualsnot grpmax-eligible	0.00486%	20,564
Finnishnot grpmax-eligible	0.00318%	31,475
European (non-Finnish)	0.00273%	36,578
East Asian	0.00223%	44,870
African / African-American	0.00134%	74,628

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.Gly343Ser
Coding: c.1027G>A
MANE Select: NM_001620
Type: single nucleotide variant
Location: chr11:62533390 (GRCh38)
Gene constraint: LOEUF 0.793 · pLI <0.01 (gnomAD)
Residue 343: the 'disordered' region

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

Similar variants

AHNAK p.Asn3289His Uncertain significance ★★ ⚠ same type
AHNAK p.Gly365Val Uncertain significance ★★ ⚠ same type
AHNAK p.Ala3588= Benign/Likely benign ★★ same type
AHNAK p.Arg1063Lys Benign ★★ same type
AHNAK p.Arg1272Pro Benign ★★ same type
AHNAK p.Asn3587Ser Benign ★★ same type
AHNAK p.Asp1493= Benign ★★ same type
AHNAK p.Asp2459= Benign ★★ same type

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-gly343ser (accessed [today's date]).

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