Is EBLN2 p.Ile103Val (c.307A>G) pathogenic?

EBLN2 p.Ile103Val (c.307A>G) is classified Uncertain significance in EBLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.2256); Very rare (popmax 0.00667%, sas).

How common is EBLN2 p.Ile103Val (c.307A>G) in the general population?

EBLN2 p.Ile103Val (c.307A>G) is very rare (popmax 0.00667%, sas) (gnomAD).

What do computational predictors say about EBLN2 p.Ile103Val (c.307A>G)?

AlphaMissense predicts likely benign (score 0.2256) — an in-silico prediction, not a clinical call.

EBLN2 p.Ile103Val

c.307A>G · VCV4246282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2256 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2256	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -6.44	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 0.21	GERP -0.48, phastCons 0.009
Regional constraint	o/e 1.22	unconstrained · MANE · 815 bp · p 5.3e-05 · regional, not allelic
Overall
CADD	4.698	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 0.00667% South Asian · 6/89,992 alleles

Filtering AF 0.00289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00197%

Overall 0.00056% 9/1,607,452 alleles · very rare exomes 9/1,455,164 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00667%	14,999
European (non-Finnish)	0.000255%	392,736

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: EBLN2
Protein: p.Ile103Val
Coding: c.307A>G
MANE Select: NM_018029
Type: single nucleotide variant
Location: chr3:73062388 (GRCh38)
Gene constraint: LOEUF 1.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.89

Full EBLN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBLN2 p.Ala106Thr Uncertain significance ★ ⚠ same type
EBLN2 p.Ala107Val Uncertain significance ★ ⚠ same type
EBLN2 p.Ala165Gly Uncertain significance ★ ⚠ same type
EBLN2 p.Ala176Gly Uncertain significance ★ ⚠ same type
EBLN2 p.Ala214Val Uncertain significance ★ ⚠ same type
EBLN2 p.Arg160Gly Uncertain significance ★ ⚠ same type
EBLN2 p.Arg160Ser Uncertain significance ★ ⚠ same type
EBLN2 p.Arg184Cys 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/ebln2-p-ile103val (accessed [today's date]).

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