Is FRK p.Val161Ile (c.481G>A) pathogenic?

FRK p.Val161Ile (c.481G>A) is classified Uncertain significance in FRK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.0736); Rare (popmax 0.137%, afr).

How common is FRK p.Val161Ile (c.481G>A) in the general population?

FRK p.Val161Ile (c.481G>A) is rare (popmax 0.137%, afr) (gnomAD).

What do computational predictors say about FRK p.Val161Ile (c.481G>A)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

FRK p.Val161Ile

c.481G>A · rs143351471 · VCV2358115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.137%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -6.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP 1
Regional constraint	o/e 0.95	unconstrained · MANE · 118 kb · p 0.2 · regional, not allelic
Overall
CADD	13.49	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.137% African / African-American · 103/74,988 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00651% 105/1,612,788 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.137%	728
South Asian	0.00221%	45,343

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.Val161Ile
Coding: c.481G>A
MANE Select: NM_002031
dbSNP: rs143351471
Type: single nucleotide variant
Location: chr6:115968725 (GRCh38)
Gene constraint: LOEUF 1.016 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.41
Residue 161: the sh2 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-val161ile (accessed [today's date]).

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