Is BRCA1 p.Gln210= (c.630A>G) pathogenic?

BRCA1 p.Gln210= (c.630A>G) is classified Likely benign in BRCA1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-05). Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Gln210= (c.630A>G)?

BRCA1 p.Gln210= (c.630A>G) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, BRCA1-related cancer predisposition (ClinVar).

How common is BRCA1 p.Gln210= (c.630A>G) in the general population?

BRCA1 p.Gln210= (c.630A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

BRCA1 p.Gln210=

c.630A>G · rs1555593567 · VCV481086

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.38	acceptor loss · deltas
Pangolin	Δ0.42	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.7	GERP 0.19, phastCons 0.017
Overall
CADD	2.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,042 alleles

Overall 0.000124% 2/1,613,904 alleles · very rare exomes 2/1,461,594 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,042
European (non-Finnish)	8.48e-05%	1,179,892

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.Gln210=
Coding: c.630A>G
MANE Select: NM_007294
dbSNP: rs1555593567
Type: single nucleotide variant
Location: chr17:43095886 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB

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 BRCA1-related cancer predisposition

Similar variants

BRCA1 p.Gln210Ter Uncertain significance ★★★ same residue
BRCA1 p.Gln210Arg Uncertain significance ★★ ⚠ same residue
BRCA1 p.Gln210Glu Uncertain significance ★ ⚠ 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
BRCA1 c.212+1G>T Pathogenic ★★★ same condition
BRCA1 c.212+3A>G 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-gln210 (accessed [today's date]).

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