Is EBLN1 p.Arg138Pro (c.413G>C) pathogenic?

EBLN1 p.Arg138Pro (c.413G>C) is classified Uncertain significance in EBLN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-29). AlphaMissense: ambiguous (0.4976); Absent from gnomAD v4.1.

How common is EBLN1 p.Arg138Pro (c.413G>C) in the general population?

EBLN1 p.Arg138Pro (c.413G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBLN1 p.Arg138Pro (c.413G>C)?

AlphaMissense predicts ambiguous (score 0.4976) — an in-silico prediction, not a clinical call.

EBLN1 p.Arg138Pro

c.413G>C · rs765282974 · VCV2298705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4976	ambiguous · top 7% in EBLN1
SaProt	LLR -8.39	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5	GERP -0.48
Regional constraint	o/e 0.88	unconstrained · MANE · 1,097 bp · p 0.014 · regional, not allelic
Overall
CADD	0.154	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EBLN1
Protein: p.Arg138Pro
Coding: c.413G>C
MANE Select: NM_001394757
dbSNP: rs765282974
Type: single nucleotide variant
Location: chr10:22209571 (GRCh38)
Gene constraint: LOEUF 1.908 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.45

Full EBLN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBLN1 p.Ala148Val Uncertain significance ★ ⚠ same type
EBLN1 p.Ala218Val Uncertain significance ★ ⚠ same type
EBLN1 p.Ala256Thr Uncertain significance ★ ⚠ same type
EBLN1 p.Ala302Glu Uncertain significance ★ same type
EBLN1 p.Ala305Gly Uncertain significance ★ ⚠ same type
EBLN1 p.Ala309Asp Uncertain significance ★ same type
EBLN1 p.Arg199Ser Uncertain significance ★ same type
EBLN1 p.Arg358Cys 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/ebln1-p-arg138pro (accessed [today's date]).

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