Is SCARF2 p.Pro647Ser (c.1939C>T) pathogenic?

SCARF2 p.Pro647Ser (c.1939C>T) is classified Uncertain significance in SCARF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely benign (0.115); Very rare (popmax 0.0014%, afr); Associated with Inborn genetic diseases.

What condition is associated with SCARF2 p.Pro647Ser (c.1939C>T)?

SCARF2 p.Pro647Ser (c.1939C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SCARF2 p.Pro647Ser (c.1939C>T) in the general population?

SCARF2 p.Pro647Ser (c.1939C>T) is very rare (popmax 0.0014%, afr) (gnomAD).

What do computational predictors say about SCARF2 p.Pro647Ser (c.1939C>T)?

AlphaMissense predicts likely benign (score 0.115) — an in-silico prediction, not a clinical call.

SCARF2 p.Pro647Ser

c.1939C>T · VCV3437932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.115 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0014%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.115	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 0.95, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 3,952 bp · p 0.87 · regional, not allelic
Overall
CADD	26.7	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P652S vs ClinVar P647S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0014% African / African-American · 1/71,610 alleles

Overall 6.34e-05% 1/1,577,216 alleles · very rare exomes 1/1,425,116 · genomes 0/152,100 · 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.Pro647Ser
Coding: c.1939C>T
MANE Select: NM_182895
Type: single nucleotide variant
Location: chr22:20426037 (GRCh38)
Gene constraint: LOEUF 0.992 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.63
Residue 652 UniProt numbering: the 'disordered' region

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-pro647ser (accessed [today's date]).

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