Is BRICD5 p.Pro199Thr (c.595C>A) pathogenic?

BRICD5 p.Pro199Thr (c.595C>A) is classified Uncertain significance in BRICD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: likely benign (0.1252); Absent from gnomAD v4.1.

How common is BRICD5 p.Pro199Thr (c.595C>A) in the general population?

BRICD5 p.Pro199Thr (c.595C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRICD5 p.Pro199Thr (c.595C>A)?

AlphaMissense predicts likely benign (score 0.1252) — an in-silico prediction, not a clinical call.

BRICD5 p.Pro199Thr

c.595C>A · VCV3825624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1252 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1252	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.3, phastCons 1
Regional constraint	o/e 1.47	unconstrained · MANE · 1,468 bp · p 8.7e-17 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P231T vs ClinVar P199T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRICD5
Protein: p.Pro199Thr
Coding: c.595C>A
MANE Select: NM_182563
Type: single nucleotide variant
Location: chr16:2209454 (GRCh38)
Gene constraint: LOEUF 1.976 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.89

Full BRICD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRICD5 p.Pro199Ser Uncertain significance ★ ⚠ same residue
BRICD5 p.Ala43Asp Uncertain significance ★ ⚠ same type
BRICD5 p.Ala43Val Uncertain significance ★ ⚠ same type
BRICD5 p.Ala90Thr Uncertain significance ★ ⚠ same type
BRICD5 p.Arg10Cys Uncertain significance ★ ⚠ same type
BRICD5 p.Arg118Cys Uncertain significance ★ ⚠ same type
BRICD5 p.Arg118His Uncertain significance ★ ⚠ same type
BRICD5 p.Arg128His Uncertain significance ★ ⚠ 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/bricd5-p-pro199thr (accessed [today's date]).

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