Is SCAF4 p.Pro296Arg (c.887C>G) pathogenic?

SCAF4 p.Pro296Arg (c.887C>G) is classified Conflicting classifications of pathogenicity in SCAF4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-01). AlphaMissense: likely benign (0.1582); Ultra-rare (popmax 0.0318%, sas); Associated with Inborn genetic diseases.

What condition is associated with SCAF4 p.Pro296Arg (c.887C>G)?

SCAF4 p.Pro296Arg (c.887C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SCAF4 p.Pro296Arg (c.887C>G) in the general population?

SCAF4 p.Pro296Arg (c.887C>G) is ultra-rare (popmax 0.0318%, sas) (gnomAD).

What do computational predictors say about SCAF4 p.Pro296Arg (c.887C>G)?

AlphaMissense predicts likely benign (score 0.1582) — an in-silico prediction, not a clinical call.

SCAF4 p.Pro296Arg

c.887C>G · rs748174835 · VCV2560816

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1582 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0318%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1582	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -11.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 2,491 bp · p 0.073 · regional, not allelic
Overall
CADD	19.82	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 0.0318% South Asian · 29/91,082 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.00204% 33/1,613,888 alleles · ultra-rare exomes 32/1,461,732 · genomes 1/152,156 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0318%	3,141
Remaining individualsnot grpmax-eligible	0.0048%	20,826
European (non-Finnish)	8.47e-05%	1,179,942

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.Pro296Arg
Coding: c.887C>G
MANE Select: NM_020706
dbSNP: rs748174835
Type: single nucleotide variant
Location: chr21:31696641 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.53 · 1 PDB
Residue 296: 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.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
SCAF4 p.Ile575Val Likely benign ★★ 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-pro296arg (accessed [today's date]).

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