Is AHNAK p.Ser412Ile (c.1235G>T) pathogenic?

AHNAK p.Ser412Ile (c.1235G>T) is classified Benign in AHNAK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). AlphaMissense: likely benign (0.117); Rare (popmax 0.83%, amr).

How common is AHNAK p.Ser412Ile (c.1235G>T) in the general population?

AHNAK p.Ser412Ile (c.1235G>T) is rare (popmax 0.83%, amr) (gnomAD).

What do computational predictors say about AHNAK p.Ser412Ile (c.1235G>T)?

AlphaMissense predicts likely benign (score 0.117) — an in-silico prediction, not a clinical call.

AHNAK p.Ser412Ile

c.1235G>T · rs202011056 · VCV721119

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.117 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.83%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.117	likely benign
REVEL	0.038	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 -4.1	GERP -4
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.28 · regional, not allelic
Overall
CADD	0.02	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 0.83% Admixed American · 369/44,454 alleles

Filtering AF 0.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.733%

Overall 0.027% 414/1,531,764 alleles · rare exomes 365/1,379,420 · genomes 49/152,344 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.83%	120
Middle Eastern	0.0354%	2,823
Remaining individualsnot grpmax-eligible	0.0204%	4,902
South Asian	0.0171%	5,838
East Asian	0.0045%	22,200
African / African-American	0.00417%	23,988
European (non-Finnish)	0.00114%	88,101

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.Ser412Ile
Coding: c.1235G>T
MANE Select: NM_001620
dbSNP: rs202011056
Type: single nucleotide variant
Location: chr11:62533182 (GRCh38)
Gene constraint: LOEUF 0.793 · pLI <0.01 (gnomAD)

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-ser412ile (accessed [today's date]).

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