Is ZBED4 p.Ser76Phe (c.227C>T) pathogenic?

ZBED4 p.Ser76Phe (c.227C>T) is classified Uncertain significance in ZBED4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). AlphaMissense: likely benign (0.0996); No allele count reported in gnomAD v4.1 (AN 1,607,114).

How common is ZBED4 p.Ser76Phe (c.227C>T) in the general population?

ZBED4 p.Ser76Phe (c.227C>T) is no allele count reported in gnomAD v4.1 (AN 1,607,114) (gnomAD).

What do computational predictors say about ZBED4 p.Ser76Phe (c.227C>T)?

AlphaMissense predicts likely benign (score 0.0996) — an in-silico prediction, not a clinical call.

ZBED4 p.Ser76Phe

c.227C>T · rs2519218514 · VCV2532410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0996 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,114)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0996	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -7.95	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 2.8	GERP 0.66, phastCons 0.035
Regional constraint	o/e 0.92	unconstrained · MANE · 952 bp · p 0.098 · regional, not allelic
Overall
CADD	16.25	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

No allele count reported in gnomAD v4.1 (AN 1,607,114). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ZBED4
Protein: p.Ser76Phe
Coding: c.227C>T
MANE Select: NM_014838
dbSNP: rs2519218514
Type: single nucleotide variant
Location: chr22:49883889 (GRCh38)
Gene constraint: LOEUF 0.729 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 67.86

Full ZBED4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ZBED4 p.Ala59= Benign ★★ same type
ZBED4 p.Asn810= Benign ★★ same type
ZBED4 p.Met1150Thr Benign ★★ same type
ZBED4 p.Ser824= Benign ★★ same type
ZBED4 p.Thr575= Benign ★★ same type
ZBED4 p.Ala1051Val Uncertain significance ★ ⚠ same type
ZBED4 p.Ala1060Thr Uncertain significance ★ ⚠ same type
ZBED4 p.Ala1060Val 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/zbed4-p-ser76phe (accessed [today's date]).

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