Is BRCA1 p.Phe1571Ser (c.4712T>C) pathogenic?

BRCA1 p.Phe1571Ser (c.4712T>C) is classified Conflicting classifications of pathogenicity in BRCA1 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-06-09). AlphaMissense: ambiguous (0.5291); Very rare (popmax 0.000254%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Phe1571Ser (c.4712T>C)?

BRCA1 p.Phe1571Ser (c.4712T>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Phe1571Ser (c.4712T>C) in the general population?

BRCA1 p.Phe1571Ser (c.4712T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about BRCA1 p.Phe1571Ser (c.4712T>C)?

AlphaMissense predicts ambiguous (score 0.5291) — an in-silico prediction, not a clinical call.

BRCA1 p.Phe1571Ser

c.4712T>C · rs273901740 · VCV55268

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

ambiguous

0.5291 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5291	ambiguous · top 8% in BRCA1
REVEL	0.676	pathogenic-leaning
SaProt	LLR -5.11	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	22.5	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 0.000254% European (non-Finnish) · 3/1,180,032 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,884 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.Phe1571Ser
Coding: c.4712T>C
MANE Select: NM_007294
dbSNP: rs273901740
Type: single nucleotide variant
Location: chr17:43071202 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1571: the 'disordered' region; a UniProt-annotated variant site (in fancs)

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

Disease context

hereditary neoplastic syndrome — 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

Similar variants

BRCA1 p.Phe1571Ile Uncertain significance ★★ ⚠ same residue
BRCA1 p.Phe1571Leu Uncertain significance ★ ⚠ same residue
BRCA1 p.Phe1571fs Pathogenic ★★★ same residue
BRCA1 p.Phe1571_Ser1572insTer Pathogenic ★★ same residue
BRCA1 p.Phe1571= Likely benign ★ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
BRCA1 c.135-1G>T Pathogenic ★★★ same condition
BRCA1 c.212+1G>A 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-phe1571ser (accessed [today's date]).

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