Is EBLN2 p.Ile175Val (c.523A>G) pathogenic?

EBLN2 p.Ile175Val (c.523A>G) is classified Uncertain significance in EBLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-12). AlphaMissense: likely benign (0.1081); Very rare (popmax 0.00203%, nfe).

How common is EBLN2 p.Ile175Val (c.523A>G) in the general population?

EBLN2 p.Ile175Val (c.523A>G) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about EBLN2 p.Ile175Val (c.523A>G)?

AlphaMissense predicts likely benign (score 0.1081) — an in-silico prediction, not a clinical call.

EBLN2 p.Ile175Val

c.523A>G · rs753648597 · VCV2411323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1081 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1081	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -3.30	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 0.16	GERP 0.19, phastCons 0.002
Regional constraint	o/e 1.22	unconstrained · MANE · 815 bp · p 5.3e-05 · regional, not allelic
Overall
CADD	4.105	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 0.00203% European (non-Finnish) · 24/1,179,902 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00161% 26/1,613,900 alleles · very rare exomes 25/1,461,690 · genomes 1/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,163
Remaining individualsnot grpmax-eligible	0.0016%	62,464
South Asian	0.0011%	91,090

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.Ile175Val
Coding: c.523A>G
MANE Select: NM_018029
dbSNP: rs753648597
Type: single nucleotide variant
Location: chr3:73062604 (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-ile175val (accessed [today's date]).

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