Is CAP1 p.Lys170Arg (c.509A>G) pathogenic?

CAP1 p.Lys170Arg (c.509A>G) is classified Uncertain significance in CAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.18); Very rare (popmax 0.00223%, eas).

How common is CAP1 p.Lys170Arg (c.509A>G) in the general population?

CAP1 p.Lys170Arg (c.509A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CAP1 p.Lys170Arg (c.509A>G)?

AlphaMissense predicts likely benign (score 0.18) — an in-silico prediction, not a clinical call.

CAP1 p.Lys170Arg

c.509A>G · VCV3995098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.18 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.18	likely benign
REVEL	0.346	indeterminate
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 12 kb · p 1.1e-11 · regional, not allelic
Overall
CADD	26.4	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 0.00223% East Asian · 1/44,878 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000753% 11/1,460,144 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
European (non-Finnish)	0.000848%	117,899

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: CAP1
Protein: p.Lys170Arg
Coding: c.509A>G
MANE Select: NM_006367
Type: single nucleotide variant
Location: chr1:40064544 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.85 · 5 PDB

Full CAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAP1 p.Ala73= Benign ★★ same type
CAP1 p.Tyr31= Benign ★★ same type
CAP1 p.Ala145Ser Uncertain significance ★ ⚠ same type
CAP1 p.Ala161Ser Uncertain significance ★ ⚠ same type
CAP1 p.Ala259Ser Uncertain significance ★ ⚠ same type
CAP1 p.Ala259Thr Uncertain significance ★ ⚠ same type
CAP1 p.Ala270Gly Uncertain significance ★ ⚠ same type
CAP1 p.Ala302Val 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/cap1-p-lys170arg (accessed [today's date]).

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