Is ARFGAP2 p.Lys15Glu (c.43A>G) pathogenic?

ARFGAP2 p.Lys15Glu (c.43A>G) is classified Uncertain significance in ARFGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely pathogenic (0.9432); Ultra-rare (popmax 0.0132%, sas).

How common is ARFGAP2 p.Lys15Glu (c.43A>G) in the general population?

ARFGAP2 p.Lys15Glu (c.43A>G) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about ARFGAP2 p.Lys15Glu (c.43A>G)?

AlphaMissense predicts likely pathogenic (score 0.9432) — an in-silico prediction, not a clinical call.

ARFGAP2 p.Lys15Glu

c.43A>G · VCV3936670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9432 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9432	likely pathogenic
REVEL	0.251	benign-leaning
SaProt	LLR -13.62	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.12 · regional, not allelic
Overall
CADD	26.3	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 0.0132% South Asian · 12/91,086 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.000958% 14/1,461,736 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,590
East Asian	0.00223%	44,854
Remaining individualsnot grpmax-eligible	0.0016%	62,500

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: ARFGAP2
Protein: p.Lys15Glu
Coding: c.43A>G
MANE Select: NM_032389
Type: single nucleotide variant
Location: chr11:47176811 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.19 · 1 PDB
Residue 15: the arf-gap domain; an α-helix

Full ARFGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARFGAP2 p.Ala227Thr Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala259Thr Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala266Val Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala272Thr Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala421Val Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala443Val Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala500Pro Uncertain significance ★ ⚠ same type
ARFGAP2 p.Arg119Trp 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/arfgap2-p-lys15glu (accessed [today's date]).

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