Is EMILIN2 p.Ser613Phe (c.1838C>T) pathogenic?

EMILIN2 p.Ser613Phe (c.1838C>T) is classified Uncertain significance in EMILIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1344); Ultra-rare (popmax 0.04%, afr).

How common is EMILIN2 p.Ser613Phe (c.1838C>T) in the general population?

EMILIN2 p.Ser613Phe (c.1838C>T) is ultra-rare (popmax 0.04%, afr) (gnomAD).

What do computational predictors say about EMILIN2 p.Ser613Phe (c.1838C>T)?

AlphaMissense predicts likely benign (score 0.1344) — an in-silico prediction, not a clinical call.

EMILIN2 p.Ser613Phe

c.1838C>T · VCV4248682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1344 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1344	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -8.84	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 3.1	GERP 1.2, phastCons 0.43
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.34 · regional, not allelic
Overall
CADD	13.93	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 0.04% African / African-American · 30/75,050 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00198% 32/1,614,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.04%	2,502
Remaining individualsnot grpmax-eligible	0.0032%	31,252

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.Ser613Phe
Coding: c.1838C>T
MANE Select: NM_032048
Type: single nucleotide variant
Location: chr18:2891965 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.88

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-ser613phe (accessed [today's date]).

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