Is AFAP1L2 p.Glu602Lys (c.1804G>A) pathogenic?

AFAP1L2 p.Glu602Lys (c.1804G>A) is classified Uncertain significance in AFAP1L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0854); Ultra-rare (popmax 0.012%, afr).

How common is AFAP1L2 p.Glu602Lys (c.1804G>A) in the general population?

AFAP1L2 p.Glu602Lys (c.1804G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about AFAP1L2 p.Glu602Lys (c.1804G>A)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

AFAP1L2 p.Glu602Lys

c.1804G>A · VCV4247287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.04	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 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 8,830 bp · p 0.56 · regional, not allelic
Overall
CADD	20.2	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 0.012% African / African-American · 9/75,046 alleles

Filtering AF 0.00622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.000929% 15/1,614,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,338
European (non-Finnish)	0.000508%	196,669

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: AFAP1L2
Protein: p.Glu602Lys
Coding: c.1804G>A
MANE Select: NM_001001936
Type: single nucleotide variant
Location: chr10:114300347 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.56 · 1 PDB

Full AFAP1L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AFAP1L2 p.Arg648His Uncertain significance ★★ ⚠ same type
AFAP1L2 p.Arg730= Benign/Likely benign ★★ same type
VWA2 p.Arg682Trp Benign ★★ ⚠ same type
VWA2 p.Asn331= Benign ★★ same type
VWA2 p.Gly641= Likely benign ★★ same type
VWA2 p.His496Tyr Benign ★★ same type
VWA2 p.Phe365= Benign ★★ same type
VWA2 p.Pro544= Benign ★★ 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/afap1l2-p-glu602lys (accessed [today's date]).

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