Is BRCA1 p.Arg71Ser (c.213G>T) pathogenic?

BRCA1 p.Arg71Ser (c.213G>T) is classified Uncertain significance in BRCA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-08-09). AlphaMissense: likely pathogenic (0.9817); Very rare (popmax 8.48e-05%, nfe).

How common is BRCA1 p.Arg71Ser (c.213G>T) in the general population?

BRCA1 p.Arg71Ser (c.213G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about BRCA1 p.Arg71Ser (c.213G>T)?

AlphaMissense predicts likely pathogenic (score 0.9817) — an in-silico prediction, not a clinical call.

BRCA1 p.Arg71Ser

c.213G>T · rs1441240938 · VCV867971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9817 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9817	likely pathogenic · top 1% in BRCA1
REVEL	0.718	pathogenic-leaning
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.74	acceptor loss · deltas
Pangolin	Δ0.47	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.93	GERP -5.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	19.68	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 8.48e-05% European (non-Finnish) · 1/1,179,000 alleles

Overall 6.85e-05% 1/1,460,318 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: BRCA1
Protein: p.Arg71Ser
Coding: c.213G>T
MANE Select: NM_007294
dbSNP: rs1441240938
Type: single nucleotide variant
Location: chr17:43104956 (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

Similar variants

BRCA1 p.Arg71Gly Pathogenic ★★★ same residue
BRCA1 p.Arg71Lys 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.Arg71= Uncertain significance ★ same residue
BRCA1 p.Arg71fs Pathogenic ★★★ same residue
BRCA1 c.134+3A>T Likely 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/brca1-p-arg71ser (accessed [today's date]).

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