Is SCAF4 p.Pro251Arg (c.752C>G) pathogenic?

SCAF4 p.Pro251Arg (c.752C>G) is classified Likely benign in SCAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely benign (0.2016); Ultra-rare (popmax 0.0201%, eas); Associated with Inborn genetic diseases.

What condition is associated with SCAF4 p.Pro251Arg (c.752C>G)?

SCAF4 p.Pro251Arg (c.752C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SCAF4 p.Pro251Arg (c.752C>G) in the general population?

SCAF4 p.Pro251Arg (c.752C>G) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about SCAF4 p.Pro251Arg (c.752C>G)?

AlphaMissense predicts likely benign (score 0.2016) — an in-silico prediction, not a clinical call.

SCAF4 p.Pro251Arg

c.752C>G · rs747668522 · VCV3158176

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2016	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -9.65	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 10	GERP 2.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,343 bp · p 0.16 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,874 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00062% 10/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,986
African / African-American	0.00134%	74,890

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: SCAF4
Protein: p.Pro251Arg
Coding: c.752C>G
MANE Select: NM_020706
dbSNP: rs747668522
Type: single nucleotide variant
Location: chr21:31701020 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.53 · 1 PDB
Residue 251: a UniProt-annotated variant site (in fzs; likely pathogenic); the 'disordered' region

Full SCAF4 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

SCAF4 p.Pro251Ser Uncertain significance ★ ⚠ same residue
SCAF4 p.Arg71Gln Uncertain significance ★★ ⚠ same condition
SCAF4 p.Asn627Ser Uncertain significance ★★ ⚠ same condition
SCAF4 p.Lys635Glu Uncertain significance ★★ ⚠ same condition
SCAF4 p.Pro330Ala Uncertain significance ★★ ⚠ same condition
SCAF4 p.Ser139Gly Uncertain significance ★★ ⚠ same condition
SCAF4 p.Ser397Ala Uncertain significance ★★ ⚠ same condition
SCAF4 p.Val916Ile 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/scaf4-p-pro251arg (accessed [today's date]).

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