Is AHNAK p.Arg102His (c.305G>A) pathogenic?

AHNAK p.Arg102His (c.305G>A) is classified Likely benign in AHNAK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0688); Ultra-rare (popmax 0.045%, sas).

How common is AHNAK p.Arg102His (c.305G>A) in the general population?

AHNAK p.Arg102His (c.305G>A) is ultra-rare (popmax 0.045%, sas) (gnomAD).

What do computational predictors say about AHNAK p.Arg102His (c.305G>A)?

AlphaMissense predicts likely benign (score 0.0688) — an in-silico prediction, not a clinical call.

AHNAK p.Arg102His

c.305G>A · rs192578949 · VCV2408353

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0688 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0688	likely benign
REVEL	0.049	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 4.2	GERP 0.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.28 · regional, not allelic
Overall
CADD	19.1	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 0.045% South Asian · 41/91,062 alleles

Filtering AF 0.0341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00701% 113/1,613,124 alleles · ultra-rare exomes 84/1,460,784 · genomes 29/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.045%	2,221
Admixed American	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.0176%	5,677
African / African-American	0.004%	25,015
European (non-Finnish)	0.00263%	38,040

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.Arg102His
Coding: c.305G>A
MANE Select: NM_001620
dbSNP: rs192578949
Type: single nucleotide variant
Location: chr11:62535040 (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-arg102his (accessed [today's date]).

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