Is ARFGEF2 p.Ser700= (c.2100C>T) pathogenic?

ARFGEF2 p.Ser700= (c.2100C>T) is classified Likely benign in ARFGEF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-22). Ultra-rare (popmax 0.0855%, afr).

How common is ARFGEF2 p.Ser700= (c.2100C>T) in the general population?

ARFGEF2 p.Ser700= (c.2100C>T) is ultra-rare (popmax 0.0855%, afr) (gnomAD).

ARFGEF2 p.Ser700=

c.2100C>T · rs145085689 · VCV389701

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0855%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.62	GERP -1.5, phastCons 0.097
Overall
CADD	9.644	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0855% African / African-American · 64/74,892 alleles

Filtering AF 0.0687% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0625%

Overall 0.00539% 87/1,613,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0855%	1,170
Admixed American	0.00333%	29,989
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.00161%	62,107

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: ARFGEF2
Protein: p.Ser700=
Coding: c.2100C>T
MANE Select: NM_006420
dbSNP: rs145085689
Type: single nucleotide variant
Location: chr20:48985437 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.59 · 2 PDB
Residue 700: the sec7 domain; a modified residue (phosphoserine)

Full ARFGEF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARFGEF2 p.Ser700Asn Uncertain significance ★ ⚠ same residue
ARFGEF2 c.4315+5T>G Uncertain significance ★★ same type
ARFGEF2 c.4316-12T>C Uncertain significance ★★ same type
ARFGEF2 c.*368A>G Uncertain significance ★★ same type
ARFGEF2 p.Ala270Thr Uncertain significance ★★ ⚠ same type
ARFGEF2 p.Ala701Thr Uncertain significance ★★ ⚠ same type
ARFGEF2 p.Arg1012Cys Uncertain significance ★★ ⚠ same type
ARFGEF2 p.Arg1012His 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/arfgef2-p-ser700 (accessed [today's date]).

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