Is AK7 p.Asp492= (c.1476C>T) pathogenic?

AK7 p.Asp492= (c.1476C>T) is classified Likely benign in AK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). Ultra-rare (popmax 0.0195%, amr).

How common is AK7 p.Asp492= (c.1476C>T) in the general population?

AK7 p.Asp492= (c.1476C>T) is ultra-rare (popmax 0.0195%, amr) (gnomAD).

AK7 p.Asp492=

c.1476C>T · rs530398565 · VCV1588443

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.53	GERP -4.8, phastCons 0.008
Overall
CADD	3.333	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0195% Admixed American · 10/51,228 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00806%

Overall 0.00115% 18/1,565,224 alleles · ultra-rare exomes 8/1,413,180 · genomes 10/152,044 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0195%	5,123
East Asian	0.0163%	6,148
African / African-American	0.00137%	72,802

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: AK7
Protein: p.Asp492=
Coding: c.1476C>T
MANE Select: NM_152327
dbSNP: rs530398565
Type: single nucleotide variant
Location: chr14:96471596 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 492: the 'adenylate kinase' region

Full AK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AK7 p.Asp492Tyr Uncertain significance ★ ⚠ same residue
AK7 p.Ala626Val Uncertain significance ★★ ⚠ same type
AK7 p.Ala675Val Uncertain significance ★★ ⚠ same type
AK7 p.Arg108His Uncertain significance ★★ ⚠ same type
AK7 p.Arg341Gln Uncertain significance ★★ ⚠ same type
AK7 p.Arg552Gln Uncertain significance ★★ ⚠ same type
AK7 p.Arg629Gln Uncertain significance ★★ ⚠ same type
AK7 p.Arg632Gly Uncertain significance ★★ ⚠ 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/ak7-p-asp492 (accessed [today's date]).

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