Is AHNAK2 p.Ala950Val (c.2849C>T) pathogenic?

AHNAK2 p.Ala950Val (c.2849C>T) is classified Likely benign in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0994); Ultra-rare (popmax 0.0496%, mid).

How common is AHNAK2 p.Ala950Val (c.2849C>T) in the general population?

AHNAK2 p.Ala950Val (c.2849C>T) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

What do computational predictors say about AHNAK2 p.Ala950Val (c.2849C>T)?

AlphaMissense predicts likely benign (score 0.0994) — an in-silico prediction, not a clinical call.

AHNAK2 p.Ala950Val

c.2849C>T · VCV4639383

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0994 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0994	likely benign
REVEL	0.024	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 -20	GERP -1.8
Regional constraint	o/e 1.23	unconstrained · MANE · 32 kb · p 4.7e-50 · regional, not allelic
Overall
CADD	0.034	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 0.0496% Middle Eastern · 3/6,054 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.00353% 57/1,612,484 alleles · ultra-rare exomes 46/1,461,356 · genomes 11/151,128 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,018
African / African-American	0.0283%	3,539
South Asian	0.00549%	18,203
Admixed American	0.00501%	19,973
East Asian	0.00447%	22,372
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,560
European (non-Finnish)	0.00187%	53,617

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: AHNAK2
Protein: p.Ala950Val
Coding: c.2849C>T
MANE Select: NM_138420
Type: single nucleotide variant
Location: chr14:104952602 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Residue 950: the 'disordered' region

Full AHNAK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AHNAK2 p.Glu3598Lys Uncertain significance ★★ ⚠ same type
AHNAK2 p.Gly4376Ser Uncertain significance ★★ ⚠ same type
AHNAK2 p.Lys2479Arg Uncertain significance ★★ ⚠ same type
AHNAK2 p.Lys3309Asn Uncertain significance ★★ ⚠ same type
AHNAK2 p.Val1351Met Uncertain significance ★★ ⚠ same type
AHNAK2 p.Ala1115Val Benign/Likely benign ★★ same type
AHNAK2 p.Ala1323Thr Likely benign ★★ same type
AHNAK2 p.Ala1818Thr Benign/Likely 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/ahnak2-p-ala950val (accessed [today's date]).

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