Is DSCAML1 p.Pro1986Ser (c.5956C>T) pathogenic?

DSCAML1 p.Pro1986Ser (c.5956C>T) is classified Uncertain significance in DSCAML1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-31). AlphaMissense: likely benign (0.0956); Ultra-rare (popmax 0.0716%, amr).

How common is DSCAML1 p.Pro1986Ser (c.5956C>T) in the general population?

DSCAML1 p.Pro1986Ser (c.5956C>T) is ultra-rare (popmax 0.0716%, amr) (gnomAD).

What do computational predictors say about DSCAML1 p.Pro1986Ser (c.5956C>T)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

DSCAML1 p.Pro1986Ser

c.5956C>T · rs1381143446 · VCV1387847

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0716%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.57	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 5.3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 463 bp · p 5.2e-06 · regional, not allelic
Overall
CADD	20.4	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

Grpmax group 0.0716% Admixed American · 36/50,288 alleles

Filtering AF 0.0531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0467%

Overall 0.00265% 40/1,511,576 alleles · ultra-rare exomes 30/1,359,552 · genomes 10/152,024 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0716%	1,397
Remaining individualsnot grpmax-eligible	0.00343%	29,152
Finnishnot grpmax-eligible	0.00174%	57,580
European (non-Finnish)	8.95e-05%	1,117,854

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: DSCAML1
Protein: p.Pro1986Ser
Coding: c.5956C>T
MANE Select: NM_020693
dbSNP: rs1381143446
Type: single nucleotide variant
Location: chr11:117428534 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.92 · 1 PDB
Residue 1986: the 'disordered' region

Full DSCAML1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSCAML1 p.Pro1986Leu Uncertain significance ★ ⚠ same residue
DSCAML1 c.-101C>T Uncertain significance ★★ same type
DSCAML1 c.-17T>C Uncertain significance ★★ same type
DSCAML1 c.-23G>A Uncertain significance ★★ same type
DSCAML1 c.-44C>T Uncertain significance ★★ same type
DSCAML1 c.-51G>T Uncertain significance ★★ same type
DSCAML1 c.-57G>A Uncertain significance ★★ same type
DSCAML1 c.-87G>A 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/dscaml1-p-pro1986ser (accessed [today's date]).

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