Is AK7 p.Arg640= (c.1920C>T) pathogenic?

AK7 p.Arg640= (c.1920C>T) is classified Likely benign in AK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-15). Very rare (popmax 0.00439%, sas).

How common is AK7 p.Arg640= (c.1920C>T) in the general population?

AK7 p.Arg640= (c.1920C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

AK7 p.Arg640=

c.1920C>T · VCV3625633

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

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 -10	GERP -4.4
Overall
CADD	0.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,026 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.0018% 29/1,613,348 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,756
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,584
European (non-Finnish)	0.00203%	49,156

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.Arg640=
Coding: c.1920C>T
MANE Select: NM_152327
Type: single nucleotide variant
Location: chr14:96483165 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35

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

Similar variants

AK7 p.Arg640Cys Uncertain significance ★ ⚠ same residue
AK7 p.Arg640Leu 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-arg640 (accessed [today's date]).

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