Is EBLN1 p.Ser12Arg (c.36C>A) pathogenic?

EBLN1 p.Ser12Arg (c.36C>A) is classified Uncertain significance in EBLN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). AlphaMissense: ambiguous (0.3749); Very rare (popmax 0.00249%, eas).

How common is EBLN1 p.Ser12Arg (c.36C>A) in the general population?

EBLN1 p.Ser12Arg (c.36C>A) is very rare (popmax 0.00249%, eas) (gnomAD).

What do computational predictors say about EBLN1 p.Ser12Arg (c.36C>A)?

AlphaMissense predicts ambiguous (score 0.3749) — an in-silico prediction, not a clinical call.

EBLN1 p.Ser12Arg

c.36C>A · VCV3274363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00249%, eas)

Computational evidence

Protein change
AlphaMissense	0.3749	ambiguous
SaProt	LLR -6.58	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP 0.1, phastCons 0.005
Regional constraint	o/e 0.88	unconstrained · MANE · 1,097 bp · p 0.014 · regional, not allelic
Overall
CADD	3.185	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 0.00249% East Asian · 1/40,094 alleles

Overall 6.98e-05% 1/1,432,098 alleles · very rare exomes 1/1,279,896 · genomes 0/152,202 · 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.Ser12Arg
Coding: c.36C>A
MANE Select: NM_001394757
Type: single nucleotide variant
Location: chr10:22209948 (GRCh38)
Gene constraint: LOEUF 1.908 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.45
Residue 12: the 'disordered' region

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.Arg138Pro Uncertain significance ★ same type
EBLN1 p.Arg199Ser 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-ser12arg (accessed [today's date]).

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