Is BEND4 p.Asn192Ser (c.575A>G) pathogenic?

BEND4 p.Asn192Ser (c.575A>G) is classified Likely benign in BEND4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.0506); Rare (popmax 0.104%, sas).

How common is BEND4 p.Asn192Ser (c.575A>G) in the general population?

BEND4 p.Asn192Ser (c.575A>G) is rare (popmax 0.104%, sas) (gnomAD).

What do computational predictors say about BEND4 p.Asn192Ser (c.575A>G)?

AlphaMissense predicts likely benign (score 0.0506) — an in-silico prediction, not a clinical call.

BEND4 p.Asn192Ser

c.575A>G · rs191493014 · VCV2521410

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0506 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.104%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0506	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -4.69	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 -4.3	GERP -3.4
Regional constraint	o/e 1.01	unconstrained · MANE · 35 kb · p 0.85 · regional, not allelic
Overall
CADD	0.018	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 0.104% South Asian · 80/76,580 alleles

Filtering AF 0.086% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0792%

Overall 0.00812% 125/1,539,972 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.104%	957
East Asian	0.027%	3,704
Remaining individualsnot grpmax-eligible	0.0152%	6,590
African / African-American	0.00689%	14,510
Admixed American	0.00207%	48,216
European (non-Finnish)	0.00157%	63,725

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.Asn192Ser
Coding: c.575A>G
MANE Select: NM_207406
dbSNP: rs191493014
Type: single nucleotide variant
Location: chr4:42143907 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.57

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.Pro473= Likely benign ★★ 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

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-asn192ser (accessed [today's date]).

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