Is FRK p.Met269Val (c.805A>G) pathogenic?

FRK p.Met269Val (c.805A>G) is classified Uncertain significance in FRK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: likely benign (0.2417); Ultra-rare (popmax 0.0158%, amr).

How common is FRK p.Met269Val (c.805A>G) in the general population?

FRK p.Met269Val (c.805A>G) is ultra-rare (popmax 0.0158%, amr) (gnomAD).

What do computational predictors say about FRK p.Met269Val (c.805A>G)?

AlphaMissense predicts likely benign (score 0.2417) — an in-silico prediction, not a clinical call.

FRK p.Met269Val

c.805A>G · VCV3517177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2417 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2417	likely benign
REVEL	0.743	pathogenic-leaning
SaProt	LLR -6.67	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 118 kb · p 0.2 · regional, not allelic
Overall
CADD	25.5	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 0.0158% Admixed American · 8/50,530 alleles

Filtering AF 0.00778% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00569%

Overall 0.00206% 32/1,550,606 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0158%	6,316
South Asian	0.00518%	19,313
African / African-American	0.00411%	24,323
Ashkenazi Jewishnot grpmax-eligible	0.00358%	27,944
East Asian	0.00233%	42,966
Remaining individualsnot grpmax-eligible	0.00167%	59,804
European (non-Finnish)	0.00122%	82,099

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: FRK
Protein: p.Met269Val
Coding: c.805A>G
MANE Select: NM_002031
Type: single nucleotide variant
Location: chr6:115956605 (GRCh38)
Gene constraint: LOEUF 1.016 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.41
Residue 269: the protein kinase domain

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

Similar variants

FRK p.Ala160Ser Uncertain significance ★ ⚠ same type
FRK p.Arg143Gly Uncertain significance ★ ⚠ same type
FRK p.Arg179Gln Uncertain significance ★ ⚠ same type
FRK p.Arg377Gly Uncertain significance ★ ⚠ same type
FRK p.Arg406His Uncertain significance ★ ⚠ same type
FRK p.Arg42Met Uncertain significance ★ ⚠ same type
FRK p.Arg42Ser Uncertain significance ★ ⚠ same type
FRK p.Arg89Leu 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/frk-p-met269val (accessed [today's date]).

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