Is EBLN2 p.Ser272Arg (c.814A>C) pathogenic?

EBLN2 p.Ser272Arg (c.814A>C) is classified Uncertain significance in EBLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: ambiguous (0.4793); Ultra-rare (popmax 0.0827%, sas).

How common is EBLN2 p.Ser272Arg (c.814A>C) in the general population?

EBLN2 p.Ser272Arg (c.814A>C) is ultra-rare (popmax 0.0827%, sas) (gnomAD).

What do computational predictors say about EBLN2 p.Ser272Arg (c.814A>C)?

AlphaMissense predicts ambiguous (score 0.4793) — an in-silico prediction, not a clinical call.

EBLN2 p.Ser272Arg

c.814A>C · rs748111324 · VCV2323574

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4793 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0827%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4793	ambiguous
REVEL	0.046	moderately benign-leaning
SaProt	LLR -6.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.25	GERP -0.48, phastCons 0.001
Regional constraint	o/e 1.22	unconstrained · MANE · 815 bp · p 5.3e-05 · regional, not allelic
Overall
CADD	12.99	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0827% South Asian · 75/90,700 alleles

Filtering AF 0.0676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.062%

Overall 0.00645% 104/1,611,160 alleles · ultra-rare exomes 98/1,458,820 · genomes 6/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0827%	1,209
Middle Eastern	0.0331%	3,020
Remaining individualsnot grpmax-eligible	0.0144%	6,928
Admixed American	0.00338%	29,560
European (non-Finnish)	0.00136%	73,681

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.Ser272Arg
Coding: c.814A>C
MANE Select: NM_018029
dbSNP: rs748111324
Type: single nucleotide variant
Location: chr3:73062895 (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-ser272arg (accessed [today's date]).

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