Is EMILIN2 p.Arg962Lys (c.2885G>A) pathogenic?

EMILIN2 p.Arg962Lys (c.2885G>A) is classified Uncertain significance in EMILIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-09). AlphaMissense: likely benign (0.1577); Very rare (popmax 0.00441%, nfe).

How common is EMILIN2 p.Arg962Lys (c.2885G>A) in the general population?

EMILIN2 p.Arg962Lys (c.2885G>A) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about EMILIN2 p.Arg962Lys (c.2885G>A)?

AlphaMissense predicts likely benign (score 0.1577) — an in-silico prediction, not a clinical call.

EMILIN2 p.Arg962Lys

c.2885G>A · rs200483351 · VCV2293853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1577 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1577	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -4.78	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 12	phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.34 · regional, not allelic
Overall
CADD	23.5	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 0.00441% European (non-Finnish) · 52/1,180,048 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.0213% 344/1,613,698 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.807%	124
Remaining individualsnot grpmax-eligible	0.08%	1,250
European (non-Finnish)grpmax	0.00441%	22,693
African / African-American	0.004%	24,975

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EMILIN2
Protein: p.Arg962Lys
Coding: c.2885G>A
MANE Select: NM_032048
dbSNP: rs200483351
Type: single nucleotide variant
Location: chr18:2913127 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.88
Residue 962: the c1q domain

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

Similar variants

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
EMILIN2 p.Pro657= 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-arg962lys (accessed [today's date]).

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