Is EMILIN2 p.Ala884Val (c.2651C>T) pathogenic?

EMILIN2 p.Ala884Val (c.2651C>T) is classified Uncertain significance in EMILIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely pathogenic (0.5824); Absent from gnomAD v4.1.

How common is EMILIN2 p.Ala884Val (c.2651C>T) in the general population?

EMILIN2 p.Ala884Val (c.2651C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMILIN2 p.Ala884Val (c.2651C>T)?

AlphaMissense predicts likely pathogenic (score 0.5824) — an in-silico prediction, not a clinical call.

EMILIN2 p.Ala884Val

c.2651C>T · VCV4664081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5824 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,253,904)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5824	likely pathogenic
REVEL	0.163	moderately benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.34 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,253,904). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EMILIN2
Protein: p.Ala884Val
Coding: c.2651C>T
MANE Select: NM_032048
Type: single nucleotide variant
Location: chr18:2907074 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.88
Residue 884: the collagen-like domain; the 'disordered' region

Full EMILIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMILIN2 p.Ala884Thr Uncertain significance ★ ⚠ same residue
EMILIN2 p.Ala215Thr Benign ★★ same type
EMILIN2 p.Ala455= Benign ★★ same type
EMILIN2 p.Cys1002= Benign ★★ same type
EMILIN2 p.Gly843= Benign/Likely benign ★★ same type
EMILIN2 p.Lys347= Benign ★★ same type
EMILIN2 p.Met259Val Benign ★★ same type
EMILIN2 p.Pro136Ser Benign ★★ 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/emilin2-p-ala884val (accessed [today's date]).

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