Is AK7 p.Thr96Arg (c.287C>G) pathogenic?

AK7 p.Thr96Arg (c.287C>G) is classified Uncertain significance in AK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-02). AlphaMissense: likely benign (0.1851); Very rare (popmax 0.00254%, nfe).

How common is AK7 p.Thr96Arg (c.287C>G) in the general population?

AK7 p.Thr96Arg (c.287C>G) is very rare (popmax 0.00254%, nfe) (gnomAD).

What do computational predictors say about AK7 p.Thr96Arg (c.287C>G)?

AlphaMissense predicts likely benign (score 0.1851) — an in-silico prediction, not a clinical call.

AK7 p.Thr96Arg

c.287C>G · rs780592470 · VCV3020703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1851 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1851	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -12.23	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.62	donor gain · deltas
Pangolin	Δ0.48	gain · loss 0.16 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4	GERP 0.83, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 96 kb · p 0.27 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% European (non-Finnish) · 30/1,179,930 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00223% 36/1,612,754 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00937%	10,669
European (non-Finnish)grpmax	0.00254%	39,331

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: AK7
Protein: p.Thr96Arg
Coding: c.287C>G
MANE Select: NM_152327
dbSNP: rs780592470
Type: single nucleotide variant
Location: chr14:96398256 (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.Thr96Ala Uncertain significance ★ ⚠ same residue
AK7 p.Thr96Met Uncertain significance ★ ⚠ same residue
AK7 p.Thr96= Likely 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

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-thr96arg (accessed [today's date]).

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