Is BRCA1 p.Arg71Lys (c.212G>A) pathogenic?

BRCA1 p.Arg71Lys (c.212G>A) is classified Pathogenic in BRCA1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2025-04-14). AlphaMissense: likely pathogenic (0.6817); No allele count reported in gnomAD v4.1 (AN 1,579,798); Associated with pancreatic cancer, susceptibility to, 4.

What condition is associated with BRCA1 p.Arg71Lys (c.212G>A)?

BRCA1 p.Arg71Lys (c.212G>A) is associated with pancreatic cancer, susceptibility to, 4, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Arg71Lys (c.212G>A) in the general population?

BRCA1 p.Arg71Lys (c.212G>A) is no allele count reported in gnomAD v4.1 (AN 1,579,798) (gnomAD).

What do computational predictors say about BRCA1 p.Arg71Lys (c.212G>A)?

AlphaMissense predicts likely pathogenic (score 0.6817) — an in-silico prediction, not a clinical call.

BRCA1 p.Arg71Lys

c.212G>A · rs80356913 · VCV54471

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely pathogenic

0.6817 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,579,798)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pancreatic cancer, susceptibility to, 4

Computational evidence

Protein change
AlphaMissense	0.6817	likely pathogenic ✓ concordant with ClinVar · top 6% in BRCA1
REVEL	0.737	pathogenic-leaning
SaProt	LLR -8.66	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.65	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.75	loss · gain 0.23 · 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

No allele count reported in gnomAD v4.1 (AN 1,579,798). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA1
Protein: p.Arg71Lys
Coding: c.212G>A
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

pancreatic cancer, susceptibility to, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 1 hereditary neoplastic syndrome Fanconi anemia, complementation group S

Similar variants

BRCA1 p.Arg71Gly Pathogenic ★★★ same residue
BRCA1 p.Arg71Met Pathogenic/Likely pathogenic ★★ same residue
BRCA1 p.Arg71Thr 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-arg71lys (accessed [today's date]).

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