Is EBLN1 p.Ser95Arg (c.283A>C) pathogenic?

EBLN1 p.Ser95Arg (c.283A>C) is classified Uncertain significance in EBLN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: ambiguous (0.5251); Very rare (popmax 0.00274%, afr).

How common is EBLN1 p.Ser95Arg (c.283A>C) in the general population?

EBLN1 p.Ser95Arg (c.283A>C) is very rare (popmax 0.00274%, afr) (gnomAD).

What do computational predictors say about EBLN1 p.Ser95Arg (c.283A>C)?

AlphaMissense predicts ambiguous (score 0.5251) — an in-silico prediction, not a clinical call.

EBLN1 p.Ser95Arg

c.283A>C · rs1229998205 · VCV2254662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5251 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00274%, afr)

Computational evidence

Protein change
AlphaMissense	0.5251	ambiguous · top 5% in EBLN1
SaProt	LLR -7.40	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -0.45
Regional constraint	o/e 0.88	unconstrained · MANE · 1,097 bp · p 0.014 · regional, not allelic
Overall
CADD	3.235	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

Grpmax group 0.00274% African / African-American · 2/73,058 alleles

Filtering AF 0.000454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00017%

Overall 0.00013% 2/1,535,782 alleles · very rare exomes 0/1,383,566 · genomes 2/152,216 · joint denominator

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: EBLN1
Protein: p.Ser95Arg
Coding: c.283A>C
MANE Select: NM_001394757
dbSNP: rs1229998205
Type: single nucleotide variant
Location: chr10:22209701 (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.Ser95Gly Uncertain significance ★ ⚠ same residue
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.Arg138Pro 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-ser95arg (accessed [today's date]).

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