Is BRCA2 p.Ile1244Phe (c.3730A>T) pathogenic?

BRCA2 p.Ile1244Phe (c.3730A>T) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-10). AlphaMissense: likely benign (0.1192); Absent from gnomAD v4.1.

How common is BRCA2 p.Ile1244Phe (c.3730A>T) in the general population?

BRCA2 p.Ile1244Phe (c.3730A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Ile1244Phe (c.3730A>T)?

AlphaMissense predicts likely benign (score 0.1192) — an in-silico prediction, not a clinical call.

BRCA2 p.Ile1244Phe

c.3730A>T · rs786202091 · VCV3253236

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1192 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.1192	likely benign
REVEL	0.592	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP -1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: BRCA2
Protein: p.Ile1244Phe
Coding: c.3730A>T
MANE Select: NM_000059
dbSNP: rs786202091
Type: single nucleotide variant
Location: chr13:32338085 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1244: the 'interaction with rad51' region

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRCA2 p.Ile1244Met Uncertain significance ★ same residue
BRCA2 p.Ile1244Thr Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ile1244Val Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ile1244= Likely benign ★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same type
BRCA2 c.316+2T>C Pathogenic ★★★ same type
BRCA2 c.316+5G>A Pathogenic ★★★ same type
BRCA2 c.316+5G>C Pathogenic ★★★ 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/brca2-p-ile1244phe (accessed [today's date]).

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