Is EBLN2 p.Ala214Val (c.641C>T) pathogenic?

EBLN2 p.Ala214Val (c.641C>T) is classified Uncertain significance in EBLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.3226); Very rare (popmax 8.48e-05%, nfe).

How common is EBLN2 p.Ala214Val (c.641C>T) in the general population?

EBLN2 p.Ala214Val (c.641C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about EBLN2 p.Ala214Val (c.641C>T)?

AlphaMissense predicts likely benign (score 0.3226) — an in-silico prediction, not a clinical call.

EBLN2 p.Ala214Val

c.641C>T · VCV3843263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3226	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Pangolin	Δ0.31	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.92	GERP -0.48, phastCons 0.005
Regional constraint	o/e 1.22	unconstrained · MANE · 815 bp · p 5.3e-05 · regional, not allelic
Overall
CADD	17.89	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 8.48e-05% European (non-Finnish) · 1/1,179,884 alleles

Overall 6.2e-05% 1/1,613,980 alleles · very rare exomes 1/1,461,684 · genomes 0/152,296 · 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: EBLN2
Protein: p.Ala214Val
Coding: c.641C>T
MANE Select: NM_018029
Type: single nucleotide variant
Location: chr3:73062722 (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.Arg160Gly Uncertain significance ★ ⚠ same type
EBLN2 p.Arg160Ser Uncertain significance ★ ⚠ same type
EBLN2 p.Arg184Cys Uncertain significance ★ ⚠ same type
EBLN2 p.Arg211Gln 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-ala214val (accessed [today's date]).

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