Is AHNAK2 p.Ala1850Val (c.5549C>T) pathogenic?

AHNAK2 p.Ala1850Val (c.5549C>T) is classified Likely benign in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: likely benign (0.0823); Ultra-rare (popmax 0.0381%, eas).

How common is AHNAK2 p.Ala1850Val (c.5549C>T) in the general population?

AHNAK2 p.Ala1850Val (c.5549C>T) is ultra-rare (popmax 0.0381%, eas) (gnomAD).

What do computational predictors say about AHNAK2 p.Ala1850Val (c.5549C>T)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

AHNAK2 p.Ala1850Val

c.5549C>T · rs199972079 · VCV2392448

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0381%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.06	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 -9.4	GERP -0.63
Regional constraint	o/e 1.23	unconstrained · MANE · 32 kb · p 4.7e-50 · regional, not allelic
Overall
CADD	0.05	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 0.0381% East Asian · 17/44,596 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0213%

Overall 0.0249% 394/1,585,362 alleles · ultra-rare exomes 363/1,441,080 · genomes 31/144,282 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.105%	955
East Asiangrpmax	0.0381%	2,623
European (non-Finnish)	0.0246%	4,063
Remaining individualsnot grpmax-eligible	0.0162%	6,158
African / African-American	0.0153%	6,519
Admixed American	0.00869%	11,504

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala1850Val
Coding: c.5549C>T
MANE Select: NM_138420
dbSNP: rs199972079
Type: single nucleotide variant
Location: chr14:104949902 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)

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

Similar variants

AHNAK2 p.Ala1850Pro Uncertain significance ★ ⚠ same residue
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

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-ala1850val (accessed [today's date]).

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