Is SCAPER p.Ser371Pro (c.1111T>C) pathogenic?

SCAPER p.Ser371Pro (c.1111T>C) is classified Likely benign in SCAPER (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.0426); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with SCAPER p.Ser371Pro (c.1111T>C)?

SCAPER p.Ser371Pro (c.1111T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SCAPER p.Ser371Pro (c.1111T>C) in the general population?

SCAPER p.Ser371Pro (c.1111T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about SCAPER p.Ser371Pro (c.1111T>C)?

AlphaMissense predicts likely benign (score 0.0426) — an in-silico prediction, not a clinical call.

SCAPER p.Ser371Pro

c.1111T>C · VCV4160234

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0426 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0426	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -6.03	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 5.1	GERP 0.26, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 117 kb · p 0.18 · regional, not allelic
Overall
CADD	12.45	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00372% 60/1,613,028 alleles · ultra-rare exomes 58/1,460,928 · genomes 2/152,100 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Admixed American	0.015%	6,665
European (non-Finnish)	0.00382%	26,210
South Asian	0.00329%	30,356
Remaining individualsnot grpmax-eligible	0.0032%	31,211

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: SCAPER
Protein: p.Ser371Pro
Coding: c.1111T>C
MANE Select: NM_020843
Type: single nucleotide variant
Location: chr15:76771879 (GRCh38)
Gene constraint: LOEUF 0.666 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.35 · 2 PDB

Full SCAPER 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

SCAPER p.Arg255Cys Uncertain significance ★★ ⚠ same condition
SCAPER p.Arg500His Uncertain significance ★★ ⚠ same condition
SCAPER p.Arg580Trp Uncertain significance ★★ ⚠ same condition
SCAPER p.Asn460Asp Uncertain significance ★★ ⚠ same condition
SCAPER p.Asp224Asn Uncertain significance ★★ ⚠ same condition
SCAPER p.Gln1353His Uncertain significance ★★ ⚠ same condition
SCAPER p.Gly264Glu Uncertain significance ★★ ⚠ same condition
SCAPER p.His1329Pro 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/scaper-p-ser371pro (accessed [today's date]).

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