Is BEGAIN p.Pro413Ser (c.1237C>T) pathogenic?

BEGAIN p.Pro413Ser (c.1237C>T) is classified Uncertain significance in BEGAIN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-06). AlphaMissense: likely benign (0.1706); Very rare (popmax 7.18e-05%).

How common is BEGAIN p.Pro413Ser (c.1237C>T) in the general population?

BEGAIN p.Pro413Ser (c.1237C>T) is very rare (popmax 7.18e-05%) (gnomAD).

What do computational predictors say about BEGAIN p.Pro413Ser (c.1237C>T)?

AlphaMissense predicts likely benign (score 0.1706) — an in-silico prediction, not a clinical call.

BEGAIN p.Pro413Ser

c.1237C>T · rs2549436475 · VCV2395657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.18e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1706	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -5.63	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 3.3	GERP 0.34, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,319 bp · p 0.52 · regional, not allelic
Overall
CADD	15.03	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P394S vs ClinVar P413S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.18e-05%

Overall 7.18e-05% 1/1,392,440 alleles · very rare

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: BEGAIN
Protein: p.Pro413Ser
Coding: c.1237C>T
MANE Select: NM_001385089
dbSNP: rs2549436475
Type: single nucleotide variant
Location: chr14:100538571 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.19

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

Similar variants

BEGAIN p.Gly388Arg Uncertain significance ★★ ⚠ same type
BEGAIN p.Asp195Asn Benign ★★ same type
BEGAIN p.Pro237Gln Benign ★★ same type
BEGAIN p.Ala194Ser Uncertain significance ★ ⚠ same type
BEGAIN p.Ala221Gly Uncertain significance ★ ⚠ same type
BEGAIN p.Ala285Gly Uncertain significance ★ ⚠ same type
BEGAIN p.Ala339Thr Uncertain significance ★ ⚠ same type
BEGAIN p.Ala454Pro 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/begain-p-pro413ser (accessed [today's date]).

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