Is EFNB1 p.Pro173Ser (c.517C>T) pathogenic?

EFNB1 p.Pro173Ser (c.517C>T) is classified Uncertain significance in EFNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: likely benign (0.1119); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EFNB1 p.Pro173Ser (c.517C>T)?

EFNB1 p.Pro173Ser (c.517C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EFNB1 p.Pro173Ser (c.517C>T) in the general population?

EFNB1 p.Pro173Ser (c.517C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFNB1 p.Pro173Ser (c.517C>T)?

AlphaMissense predicts likely benign (score 0.1119) — an in-silico prediction, not a clinical call.

EFNB1 p.Pro173Ser

c.517C>T · VCV4016586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1119 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1119	likely benign
REVEL	0.372	indeterminate
SaProt	LLR -7.76	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 5.9	GERP 0.98, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 11 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	17.62	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EFNB1
Protein: p.Pro173Ser
Coding: c.517C>T
MANE Select: NM_004429
Type: single nucleotide variant
Location: chrX:68839977 (GRCh38)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 173: the 'disordered' region

Full EFNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFNB1 p.Pro173Thr Uncertain significance ★ ⚠ same residue
EFNB1 p.Ala242Val Uncertain significance ★★ ⚠ same condition
EFNB1 p.Ala340Val Uncertain significance ★★ ⚠ same condition
EFNB1 p.Arg180Ser Uncertain significance ★★ ⚠ same condition
EFNB1 p.Arg199Trp Uncertain significance ★★ ⚠ same condition
EFNB1 p.Arg307Gln Uncertain significance ★★ ⚠ same condition
EFNB1 p.Asp206His Uncertain significance ★★ ⚠ same condition
EFNB1 p.His272Tyr Uncertain significance ★★ ⚠ same condition

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/efnb1-p-pro173ser (accessed [today's date]).

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