Is BEND4 p.Pro473= (c.1419C>T) pathogenic?

BEND4 p.Pro473= (c.1419C>T) is classified Likely benign in BEND4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-06-01). Low-frequency (popmax 1.49%, mid).

How common is BEND4 p.Pro473= (c.1419C>T) in the general population?

BEND4 p.Pro473= (c.1419C>T) is low-frequency (popmax 1.49%, mid) (gnomAD).

BEND4 p.Pro473=

c.1419C>T · rs73812731 · VCV932461

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.49%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9
Overall
CADD	1.727	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.49% Middle Eastern · 90/6,048 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.15%

Overall 0.694% 11,155/1,607,766 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.91%	52
Middle Easterngrpmax	1.49%	67
Remaining individualsnot grpmax-eligible	0.806%	124
European (non-Finnish)	0.767%	130
Admixed American	0.507%	197
African / African-American	0.311%	322
Finnishnot grpmax-eligible	0.292%	342
South Asian	0.287%	349
East Asian	0.00223%	44,764

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: BEND4
Protein: p.Pro473=
Coding: c.1419C>T
MANE Select: NM_207406
dbSNP: rs73812731
Type: single nucleotide variant
Location: chr4:42117704 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.57
Residue 473: the ben domain

Full BEND4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND4 p.Gln224Glu Uncertain significance ★★ ⚠ same type
BEND4 p.Ser268Leu Uncertain significance ★★ ⚠ same type
BEND4 p.Ala125Thr Uncertain significance ★ ⚠ same type
BEND4 p.Ala244Pro Uncertain significance ★ ⚠ same type
BEND4 p.Ala518Pro Uncertain significance ★ ⚠ same type
BEND4 p.Ala66Val Uncertain significance ★ ⚠ same type
BEND4 p.Ala82Pro Uncertain significance ★ ⚠ same type
BEND4 p.Ala94Thr 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/bend4-p-pro473 (accessed [today's date]).

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