Is AK7 p.Val425= (c.1275C>T) pathogenic?

AK7 p.Val425= (c.1275C>T) is classified Likely benign in AK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). Very rare (popmax 0.00134%, afr).

How common is AK7 p.Val425= (c.1275C>T) in the general population?

AK7 p.Val425= (c.1275C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

AK7 p.Val425=

c.1275C>T · rs113804344 · VCV2958892

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 -15	GERP -3.9
Overall
CADD	0.067	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,680 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,268 alleles · very rare exomes 9/1,461,638 · genomes 1/151,630 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,229
African / African-Americangrpmax	0.00134%	74,680
European (non-Finnish)	0.000593%	168,547

Remaining individuals 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: AK7
Protein: p.Val425=
Coding: c.1275C>T
MANE Select: NM_152327
dbSNP: rs113804344
Type: single nucleotide variant
Location: chr14:96458130 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 425: the 'adenylate kinase' region; the 'nmp' region

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

Similar variants

AK7 p.Val425Ala Uncertain significance ★ ⚠ same residue
AK7 p.Val425Phe 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

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-val425 (accessed [today's date]).

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