Is DSCAML1 p.Pro2011Ser (c.6031C>T) pathogenic?

DSCAML1 p.Pro2011Ser (c.6031C>T) is classified Uncertain significance in DSCAML1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.0941); Ultra-rare (popmax 0.092%, afr).

How common is DSCAML1 p.Pro2011Ser (c.6031C>T) in the general population?

DSCAML1 p.Pro2011Ser (c.6031C>T) is ultra-rare (popmax 0.092%, afr) (gnomAD).

What do computational predictors say about DSCAML1 p.Pro2011Ser (c.6031C>T)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

DSCAML1 p.Pro2011Ser

c.6031C>T · rs370252456 · VCV1381874

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.092%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -7.12	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 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 463 bp · p 5.2e-06 · regional, not allelic
Overall
CADD	21.4	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 0.092% African / African-American · 65/70,634 alleles

Filtering AF 0.074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0675%

Overall 0.00459% 70/1,525,080 alleles · ultra-rare exomes 28/1,375,390 · genomes 42/149,690 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.092%	1,087
Admixed American	0.00446%	22,436
Remaining individualsnot grpmax-eligible	0.00171%	58,598
European (non-Finnish)	0.000176%	568,909

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.Pro2011Ser
Coding: c.6031C>T
MANE Select: NM_020693
dbSNP: rs370252456
Type: single nucleotide variant
Location: chr11:117428459 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.92 · 1 PDB
Residue 2011: the 'disordered' region

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

Similar variants

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
DSCAML1 p.Ala1060Ser 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-pro2011ser (accessed [today's date]).

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