Is AK7 p.Arg102Ter (c.304C>T) pathogenic?

AK7 p.Arg102Ter (c.304C>T) is classified Uncertain significance in AK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-17). Very rare (popmax 0.00449%, eas).

How common is AK7 p.Arg102Ter (c.304C>T) in the general population?

AK7 p.Arg102Ter (c.304C>T) is very rare (popmax 0.00449%, eas) (gnomAD).

AK7 p.Arg102Ter

c.304C>T · rs368995788 · VCV1936307

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00449%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.12, phastCons 0.97
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% East Asian · 2/44,592 alleles

Filtering AF 0.00158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.002% 32/1,600,934 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00449%	22,296
European (non-Finnish)	0.00231%	43,308
Admixed American	0.00167%	59,844
Remaining individualsnot grpmax-eligible	0.00162%	61,824
African / African-American	0.00134%	74,738

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.Arg102Ter
Coding: c.304C>T
MANE Select: NM_152327
dbSNP: rs368995788
Type: single nucleotide variant
Location: chr14:96404766 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 102: a UniProt-annotated variant site (in)

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

Similar variants

AK7 p.Arg102Gln Benign ★★ 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-arg102ter (accessed [today's date]).

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