Is DSCAML1 p.Ala142= (c.426C>T) pathogenic?

DSCAML1 p.Ala142= (c.426C>T) is classified Likely benign in DSCAML1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). Very rare (popmax 0.00549%, sas).

How common is DSCAML1 p.Ala142= (c.426C>T) in the general population?

DSCAML1 p.Ala142= (c.426C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

DSCAML1 p.Ala142=

c.426C>T · rs372834250 · VCV1935979

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.053	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -5.5, phastCons 0.99
Overall
CADD	12.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,070 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000743% 12/1,614,026 alleles · very rare exomes 9/1,461,874 · genomes 3/152,152 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,214
European (non-Finnish)	0.000593%	168,575

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.Ala142=
Coding: c.426C>T
MANE Select: NM_020693
dbSNP: rs372834250
Type: single nucleotide variant
Location: chr11:117776876 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.92 · 1 PDB
Residue 142: the ig-like c2-type 2 domain

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

Similar variants

DSCAML1 p.Ala142Val 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-ala142 (accessed [today's date]).

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