Is DSCAML1 p.Ala2002Val (c.6005C>T) pathogenic?

DSCAML1 p.Ala2002Val (c.6005C>T) is classified Uncertain significance in DSCAML1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-01). AlphaMissense: likely benign (0.0952); Ultra-rare (popmax 0.041%, mid).

How common is DSCAML1 p.Ala2002Val (c.6005C>T) in the general population?

DSCAML1 p.Ala2002Val (c.6005C>T) is ultra-rare (popmax 0.041%, mid) (gnomAD).

What do computational predictors say about DSCAML1 p.Ala2002Val (c.6005C>T)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

DSCAML1 p.Ala2002Val

c.6005C>T · rs753302101 · VCV2085258

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.041%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -7.94	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 9.1	GERP 2.2, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 463 bp · p 5.2e-06 · regional, not allelic
Overall
CADD	22.4	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 0.041% Middle Eastern · 2/4,884 alleles

Filtering AF 0.00721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.003%

Overall 0.0015% 23/1,531,262 alleles · ultra-rare exomes 14/1,380,084 · genomes 9/151,178 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.041%	2,442
Remaining individualsnot grpmax-eligible	0.0034%	29,446
Admixed American	0.00204%	49,094
European (non-Finnish)	0.00158%	63,142

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.Ala2002Val
Coding: c.6005C>T
MANE Select: NM_020693
dbSNP: rs753302101
Type: single nucleotide variant
Location: chr11:117428485 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.92 · 1 PDB
Residue 2002: the 'disordered' region

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

Similar variants

DSCAML1 p.Ala2002Asp Uncertain significance ★★ ⚠ same residue
DSCAML1 p.Ala2002= Likely benign ★ 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

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-ala2002val (accessed [today's date]).

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