Is BEND2 p.Leu479Phe (c.1435C>T) pathogenic?

BEND2 p.Leu479Phe (c.1435C>T) is classified Uncertain significance in BEND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-14). AlphaMissense: ambiguous (0.4999); Absent from gnomAD v4.1.

How common is BEND2 p.Leu479Phe (c.1435C>T) in the general population?

BEND2 p.Leu479Phe (c.1435C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BEND2 p.Leu479Phe (c.1435C>T)?

AlphaMissense predicts ambiguous (score 0.4999) — an in-silico prediction, not a clinical call.

BEND2 p.Leu479Phe

c.1435C>T · rs1203500552 · VCV2267366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4999	ambiguous · top 9% in BEND2
REVEL	0.147	moderately benign-leaning
SaProt	LLR -9.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 50 kb · p 0.98 · regional, not allelic
Overall
CADD	21.7	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

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: BEND2
Protein: p.Leu479Phe
Coding: c.1435C>T
MANE Select: NM_153346
dbSNP: rs1203500552
Type: single nucleotide variant
Location: chrX:18177764 (GRCh38)
Structure: AlphaFold pLDDT 49.94

Full BEND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND2 p.Gln198His Benign ★★ same type
BEND2 p.Gly580Val Benign ★★ same type
BEND2 p.Ser183Ile Benign ★★ ⚠ same type
BEND2 p.Thr367= Likely benign ★★ same type
BEND2 p.Val261Gly Benign ★★ same type
BEND2 p.Ala185Gly Uncertain significance ★ ⚠ same type
BEND2 p.Ala193Thr Uncertain significance ★ ⚠ same type
BEND2 p.Ala222Ser 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/bend2-p-leu479phe (accessed [today's date]).

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