Is ARFGAP2 p.Thr8Ser (c.23C>G) pathogenic?

ARFGAP2 p.Thr8Ser (c.23C>G) is classified Uncertain significance in ARFGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely benign (0.0891); Ultra-rare (popmax 0.0167%, nfe).

How common is ARFGAP2 p.Thr8Ser (c.23C>G) in the general population?

ARFGAP2 p.Thr8Ser (c.23C>G) is ultra-rare (popmax 0.0167%, nfe) (gnomAD).

What do computational predictors say about ARFGAP2 p.Thr8Ser (c.23C>G)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

ARFGAP2 p.Thr8Ser

c.23C>G · rs772490982 · VCV3128339

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -5.87	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 5.8	GERP -0.93, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.12 · regional, not allelic
Overall
CADD	20.3	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 0.0167% European (non-Finnish) · 197/1,180,024 alleles

Filtering AF 0.0148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.0124% 200/1,613,754 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0167%	5,990
Remaining individualsnot grpmax-eligible	0.0032%	31,241
African / African-American	0.00133%	74,942

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.Thr8Ser
Coding: c.23C>G
MANE Select: NM_032389
dbSNP: rs772490982
Type: single nucleotide variant
Location: chr11:47176831 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.19 · 1 PDB
Residue 8: 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-thr8ser (accessed [today's date]).

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