Is EFNB2 p.Ser207Gly (c.619A>G) pathogenic?

EFNB2 p.Ser207Gly (c.619A>G) is classified Uncertain significance in EFNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely benign (0.0674); Very rare (popmax 0.00501%, amr).

How common is EFNB2 p.Ser207Gly (c.619A>G) in the general population?

EFNB2 p.Ser207Gly (c.619A>G) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about EFNB2 p.Ser207Gly (c.619A>G)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

EFNB2 p.Ser207Gly

c.619A>G · rs753243306 · VCV2303402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 2,723 bp · p 2.4e-05 · regional, not allelic
Overall
CADD	20.7	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 0.00501% Admixed American · 3/59,862 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000249% 4/1,608,986 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,954
Remaining individualsnot grpmax-eligible	0.00161%	62,290

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: EFNB2
Protein: p.Ser207Gly
Coding: c.619A>G
MANE Select: NM_004093
dbSNP: rs753243306
Type: single nucleotide variant
Location: chr13:106493423 (GRCh38)
Gene constraint: LOEUF 0.261 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.60 · 10 PDB
Residue 207: the 'disordered' region

Full EFNB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFNB2 p.Tyr73Ter Likely pathogenic ★ same type
EFNB2 p.Ala157Thr Uncertain significance ★ ⚠ same type
EFNB2 p.Ala296Ser Uncertain significance ★ ⚠ same type
EFNB2 p.Arg156Lys Uncertain significance ★ ⚠ same type
EFNB2 p.Arg182His Uncertain significance ★ ⚠ same type
EFNB2 p.Arg253Gln Uncertain significance ★ ⚠ same type
EFNB2 p.Arg253Trp Uncertain significance ★ ⚠ same type
EFNB2 p.Arg277Cys 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/efnb2-p-ser207gly (accessed [today's date]).

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