Is BRIP1 p.His213Arg (c.638A>G) pathogenic?

BRIP1 p.His213Arg (c.638A>G) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-08-06). AlphaMissense: likely benign (0.0719); Very rare (popmax 0.00246%, nfe); Associated with Monogenic short statue.

What condition is associated with BRIP1 p.His213Arg (c.638A>G)?

BRIP1 p.His213Arg (c.638A>G) is associated with Monogenic short statue, Fanconi anemia complementation group J, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.His213Arg (c.638A>G) in the general population?

BRIP1 p.His213Arg (c.638A>G) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about BRIP1 p.His213Arg (c.638A>G)?

AlphaMissense predicts likely benign (score 0.0719) — an in-silico prediction, not a clinical call.

BRIP1 p.His213Arg

c.638A>G · rs376760085 · VCV186617

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0719 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Monogenic short statue

Computational evidence

Protein change
AlphaMissense	0.0719	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.021	GERP -0.17, phastCons 0.3
Regional constraint	o/e 0.92	unconstrained · MANE · 68 kb · p 0.065 · regional, not allelic
Overall
CADD	13.38	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 0.00246% European (non-Finnish) · 29/1,179,876 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00199% 29/1,460,694 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: BRIP1
Protein: p.His213Arg
Coding: c.638A>G
MANE Select: NM_032043
dbSNP: rs376760085
Type: single nucleotide variant
Location: chr17:61808747 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 213: the helicase atp-binding domain

Full BRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Monogenic short statue

Also linked: Fanconi anemia complementation group J hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.His213Pro Uncertain significance ★ ⚠ same residue
BRIP1 p.His213= Likely benign ★ same residue
BRIP1 p.His213fs Pathogenic/Likely pathogenic ★★ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>C Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>G Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>T Likely pathogenic ★★ same condition
BRIP1 c.1340+1G>A Pathogenic/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/brip1-p-his213arg (accessed [today's date]).

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