Is BRCA1 p.Val626= (c.1878A>G) pathogenic?

BRCA1 p.Val626= (c.1878A>G) is classified Conflicting classifications of pathogenicity in BRCA1 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-11-09). Ultra-rare (popmax 0.0154%, sas); Associated with Fanconi anemia, complementation group S.

What condition is associated with BRCA1 p.Val626= (c.1878A>G)?

BRCA1 p.Val626= (c.1878A>G) is associated with Fanconi anemia, complementation group S, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Val626= (c.1878A>G) in the general population?

BRCA1 p.Val626= (c.1878A>G) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

BRCA1 p.Val626=

c.1878A>G · rs8176154 · VCV231250

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Conditions

Fanconi anemia, complementation group S

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.009	GERP -4.4, phastCons 0.093
Overall
CADD	4.922	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% South Asian · 14/91,086 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.0026% 42/1,614,016 alleles · ultra-rare exomes 41/1,461,816 · genomes 1/152,200 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,506
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00212%	47,200
African / African-American	0.00133%	74,926

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.Val626=
Coding: c.1878A>G
MANE Select: NM_007294
dbSNP: rs8176154
Type: single nucleotide variant
Location: chr17:43093653 (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

Fanconi anemia, complementation group S — 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

Similar variants

BRCA1 p.Val626Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Val626Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Val626Leu Conflicting classifications of pathogenicity ★ ⚠ 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-val626 (accessed [today's date]).

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