Is BEND5 p.Pro17Ser (c.49C>T) pathogenic?

BEND5 p.Pro17Ser (c.49C>T) is classified Uncertain significance in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). AlphaMissense: likely pathogenic (0.9138); Very rare (popmax 0.00208%, amr).

How common is BEND5 p.Pro17Ser (c.49C>T) in the general population?

BEND5 p.Pro17Ser (c.49C>T) is very rare (popmax 0.00208%, amr) (gnomAD).

What do computational predictors say about BEND5 p.Pro17Ser (c.49C>T)?

AlphaMissense predicts likely pathogenic (score 0.9138) — an in-silico prediction, not a clinical call.

BEND5 p.Pro17Ser

c.49C>T · VCV3824177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9138 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00208%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9138	likely pathogenic
REVEL	0.181	moderately benign-leaning
SaProt	LLR -9.69	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 200 bp · p 0.41 · regional, not allelic
Overall
CADD	29.3	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 0.00208% Admixed American · 1/48,116 alleles

Overall 0.000583% 8/1,372,948 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.018%	5,555
Remaining individualsnot grpmax-eligible	0.00339%	29,521
Admixed Americangrpmax	0.00208%	48,116

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BEND5
Protein: p.Pro17Ser
Coding: c.49C>T
MANE Select: NM_032785 · reported on NM_024603
Type: single nucleotide variant
Location: chr1:48776783 (GRCh38)

Full BEND5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/bend5-p-pro17ser (accessed [today's date]).

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