Is DSCAML1 p.Ile1226Val (c.3676A>G) pathogenic?

DSCAML1 p.Ile1226Val (c.3676A>G) is classified Uncertain significance in DSCAML1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-26). AlphaMissense: likely benign (0.1516); Very rare (popmax 0.00167%, amr).

How common is DSCAML1 p.Ile1226Val (c.3676A>G) in the general population?

DSCAML1 p.Ile1226Val (c.3676A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DSCAML1 p.Ile1226Val (c.3676A>G)?

AlphaMissense predicts likely benign (score 0.1516) — an in-silico prediction, not a clinical call.

DSCAML1 p.Ile1226Val

c.3676A>G · rs1183795222 · VCV1982053

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1516 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1516	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -5.92	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 6.1	GERP 2.6, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 53 kb · p 2.2e-14 · regional, not allelic
Overall
CADD	21.5	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 0.00167% Admixed American · 1/60,002 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000991% 16/1,614,048 alleles · very rare exomes 13/1,461,842 · genomes 3/152,206 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00119%	84,288

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.Ile1226Val
Coding: c.3676A>G
MANE Select: NM_020693
dbSNP: rs1183795222
Type: single nucleotide variant
Location: chr11:117450581 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.92 · 1 PDB
Residue 1226: the fibronectin type-iii 4 domain

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-ile1226val (accessed [today's date]).

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