Is BRCA1 p.Arg71Thr (c.212G>C) pathogenic?

BRCA1 p.Arg71Thr (c.212G>C) is classified Pathogenic/Likely pathogenic in BRCA1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-15). AlphaMissense: likely pathogenic (0.9687); Absent from gnomAD v4.1; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA1 p.Arg71Thr (c.212G>C)?

BRCA1 p.Arg71Thr (c.212G>C) is associated with hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1, hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Arg71Thr (c.212G>C) in the general population?

BRCA1 p.Arg71Thr (c.212G>C) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BRCA1 p.Arg71Thr (c.212G>C)?

AlphaMissense predicts likely pathogenic (score 0.9687) — an in-silico prediction, not a clinical call.

BRCA1 p.Arg71Thr

c.212G>C · rs80356913 · VCV267512

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.9687	likely pathogenic ✓ concordant with ClinVar · top 1% in BRCA1
REVEL	0.771	pathogenic-leaning
SaProt	LLR -11.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.65	donor loss at this position · raw score · deltas
Pangolin	Δ0.76	loss · gain 0.25 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	32.0	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

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: BRCA1
Protein: p.Arg71Thr
Coding: c.212G>C
MANE Select: NM_007294
dbSNP: rs80356913
Type: single nucleotide variant
Location: chr17:43106456 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 71: a turn; a UniProt-annotated variant site (in bc; uncertain significance)

Full BRCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: breast-ovarian cancer, familial, susceptibility to, 1 hereditary neoplastic syndrome ovarian neoplasm

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Arg71Gly Pathogenic ★★★ same residue
BRCA1 p.Arg71Lys Pathogenic ★★ same residue
BRCA1 p.Arg71Met Pathogenic/Likely pathogenic ★★ same residue
BRCA1 p.Arg71Trp Likely pathogenic ★ same residue
BRCA1 p.Arg71fs Pathogenic ★★★ same residue
BRCA1 p.Arg71= Uncertain significance ★ same residue
BRCA1 p.Arg71Ser Uncertain significance ★ ⚠ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition

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/brca1-p-arg71thr (accessed [today's date]).

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