Is AHNAK p.Arg1272Pro (c.3815G>C) pathogenic?

AHNAK p.Arg1272Pro (c.3815G>C) is classified Benign in AHNAK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-12-13). AlphaMissense: likely benign (0.0599); Low-frequency (popmax 3.78%, afr).

How common is AHNAK p.Arg1272Pro (c.3815G>C) in the general population?

AHNAK p.Arg1272Pro (c.3815G>C) is low-frequency (popmax 3.78%, afr) (gnomAD).

What do computational predictors say about AHNAK p.Arg1272Pro (c.3815G>C)?

AlphaMissense predicts likely benign (score 0.0599) — an in-silico prediction, not a clinical call.

AHNAK p.Arg1272Pro

c.3815G>C · rs115325511 · VCV783611

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0599 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.78%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0599	likely benign
REVEL	0.099	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 3.9	GERP 0.49, phastCons 0.99
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.28 · regional, not allelic
Overall
CADD	5.871	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 3.78% African / African-American · 2,689/71,164 alleles

Filtering AF 3.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.61%

Overall 0.191% 3,053/1,598,288 alleles · low-frequency exomes 1,557/1,457,212 · genomes 1,496/141,076 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.78%	26
Remaining individualsnot grpmax-eligible	0.3%	334
Middle Eastern	0.236%	424
Admixed American	0.188%	531
South Asian	0.0112%	8,961
East Asian	0.00456%	21,907
European (non-Finnish)	0.00366%	27,310

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.Arg1272Pro
Coding: c.3815G>C
MANE Select: NM_001620
dbSNP: rs115325511
Type: single nucleotide variant
Location: chr11:62530602 (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.Asn3587Ser Benign ★★ same type
AHNAK p.Asp1493= Benign ★★ same type
AHNAK p.Asp2459= Benign ★★ same type
AHNAK p.Asp2803= 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-arg1272pro (accessed [today's date]).

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