Is SCARF2 p.Pro727= (c.2181C>G) pathogenic?

SCARF2 p.Pro727= (c.2181C>G) is classified Benign in SCARF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-15). Very rare (popmax 8.97e-05%, nfe); Associated with van den Ende-Gupta syndrome.

What condition is associated with SCARF2 p.Pro727= (c.2181C>G)?

SCARF2 p.Pro727= (c.2181C>G) is associated with van den Ende-Gupta syndrome (ClinVar).

How common is SCARF2 p.Pro727= (c.2181C>G) in the general population?

SCARF2 p.Pro727= (c.2181C>G) is very rare (popmax 8.97e-05%, nfe) (gnomAD).

SCARF2 p.Pro727=

c.2181C>G · rs1171701467 · VCV1332924

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.97e-05%, nfe)

Conditions

van den Ende-Gupta syndrome

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 -2.3	GERP -0.28
Overall
CADD	4.607	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.97e-05% European (non-Finnish) · 1/1,114,358 alleles

Overall 6.81e-05% 1/1,468,196 alleles · very rare exomes 0/1,317,148 · genomes 1/151,048 · joint denominator

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: SCARF2
Protein: p.Pro727=
Coding: c.2181C>G
MANE Select: NM_182895
dbSNP: rs1171701467
Type: single nucleotide variant
Location: chr22:20425795 (GRCh38)
Gene constraint: LOEUF 0.992 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.63
Residue 727: the 'disordered' region

Full SCARF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

van den Ende-Gupta syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCARF2 p.Ala815Gly Benign ★★ same condition
SCARF2 p.Ala833Gly Benign ★★ same condition
SCARF2 p.Pro656Leu Benign/Likely benign ★★ ⚠ same condition
SCARF2 p.Cys258Tyr Likely pathogenic ★ same condition
SCARF2 p.Cys305Trp Likely pathogenic ★ same condition
SCARF2 p.Met1Ile Likely pathogenic ★ same condition
SCARF2 p.Tyr368Ter Pathogenic ★ same condition
SCARF2 p.Ala636Val Conflicting classifications of pathogenicity ★ ⚠ same condition

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/scarf2-p-pro727 (accessed [today's date]).

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