Is SCAF4 p.Pro910Ala (c.2728C>G) pathogenic?

SCAF4 p.Pro910Ala (c.2728C>G) is classified Uncertain significance in SCAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.2619); Absent from gnomAD v4.1.

How common is SCAF4 p.Pro910Ala (c.2728C>G) in the general population?

SCAF4 p.Pro910Ala (c.2728C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCAF4 p.Pro910Ala (c.2728C>G)?

AlphaMissense predicts likely benign (score 0.2619) — an in-silico prediction, not a clinical call.

SCAF4 p.Pro910Ala

c.2728C>G · VCV4086671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2619 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2619	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -9.81	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 12	GERP 2.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 760 bp · p 0.44 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SCAF4
Protein: p.Pro910Ala
Coding: c.2728C>G
MANE Select: NM_020706
Type: single nucleotide variant
Location: chr21:31672115 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.53 · 1 PDB
Residue 910: 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

Similar variants

SCAF4 p.Arg447Ter Pathogenic ★★ same type
SCAF4 p.Arg475Ter Pathogenic ★★ same type
SCAF4 p.Arg477Ter Pathogenic ★★ same type
SCAF4 p.Arg491Ter Pathogenic/Likely pathogenic ★★ same type
SOD1 p.Gly73Ser Likely pathogenic ★★ same type
SCAF4 p.Arg71Gln Uncertain significance ★★ ⚠ same type
SCAF4 p.Asn627Ser Uncertain significance ★★ ⚠ same type
SCAF4 p.Lys635Glu Uncertain significance ★★ ⚠ same type

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-pro910ala (accessed [today's date]).

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