Is SCARF2 p.Pro23Arg (c.68C>G) pathogenic?

SCARF2 p.Pro23Arg (c.68C>G) is classified Uncertain significance in SCARF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-22). AlphaMissense: likely benign (0.0743); Very rare (popmax 0.00517%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SCARF2 p.Pro23Arg (c.68C>G)?

SCARF2 p.Pro23Arg (c.68C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SCARF2 p.Pro23Arg (c.68C>G) in the general population?

SCARF2 p.Pro23Arg (c.68C>G) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about SCARF2 p.Pro23Arg (c.68C>G)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

SCARF2 p.Pro23Arg

c.68C>G · rs768621399 · VCV3158345

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.21	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 -0.09	GERP -0.67
Regional constraint	o/e 1.03	unconstrained · MANE · 5,928 bp · p 0.74 · regional, not allelic
Overall
CADD	11.29	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 0.00517% European (non-Finnish) · 58/1,121,348 alleles

Filtering AF 0.00406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00371%

Overall 0.00399% 59/1,480,120 alleles · very rare exomes 53/1,329,164 · genomes 6/150,956 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,334
Remaining individualsnot grpmax-eligible	0.00175%	57,188

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.Pro23Arg
Coding: c.68C>G
MANE Select: NM_182895
dbSNP: rs768621399
Type: single nucleotide variant
Location: chr22:20437687 (GRCh38)
Gene constraint: LOEUF 0.992 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.63

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCARF2 p.Ala12Ser Uncertain significance ★★ ⚠ same condition
SCARF2 p.Ala627Val Uncertain significance ★★ ⚠ same condition
SCARF2 p.Ala854Thr Uncertain significance ★★ ⚠ same condition
SCARF2 p.Arg860Lys Uncertain significance ★★ ⚠ same condition
SCARF2 p.Asp378Glu Uncertain significance ★★ ⚠ same condition
SCARF2 p.Asp830Asn Uncertain significance ★★ ⚠ same condition
SCARF2 p.Glu581Gln Uncertain significance ★★ ⚠ same condition
SCARF2 p.Glu853Gly Uncertain significance ★★ ⚠ 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-pro23arg (accessed [today's date]).

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