Is BAIAP3 p.Ser695Phe (c.2084C>T) pathogenic?

BAIAP3 p.Ser695Phe (c.2084C>T) is classified Uncertain significance in BAIAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-27). AlphaMissense: likely benign (0.1334); Very rare (popmax 0.00415%, afr).

How common is BAIAP3 p.Ser695Phe (c.2084C>T) in the general population?

BAIAP3 p.Ser695Phe (c.2084C>T) is very rare (popmax 0.00415%, afr) (gnomAD).

What do computational predictors say about BAIAP3 p.Ser695Phe (c.2084C>T)?

AlphaMissense predicts likely benign (score 0.1334) — an in-silico prediction, not a clinical call.

BAIAP3 p.Ser695Phe

c.2084C>T · VCV3260327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1334 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1334	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.25	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 2	GERP 0.28, phastCons 0.005
Regional constraint	o/e 1.13	unconstrained · MANE · 9,929 bp · p 2.6e-07 · regional, not allelic
Overall
CADD	13.1	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 S730F vs ClinVar S695F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00415% African / African-American · 3/72,268 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000506%

Overall 0.000386% 6/1,553,024 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00415%	24,089
European (non-Finnish)	0.000259%	385,417

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: BAIAP3
Protein: p.Ser695Phe
Coding: c.2084C>T
MANE Select: NM_001199097
Type: single nucleotide variant
Location: chr16:1345766 (GRCh38)
Gene constraint: LOEUF 1.406 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 695: the mhd1 domain

Full BAIAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAIAP3 p.Ser695Pro Uncertain significance ★ ⚠ same residue
BAIAP3 c.-11+926G>T Uncertain significance ★ ⚠ same type
BAIAP3 c.-11+983T>A Uncertain significance ★ ⚠ same type
BAIAP3 c.-11+985G>A Uncertain significance ★ ⚠ same type
BAIAP3 c.-11+991G>A Uncertain significance ★ ⚠ same type
BAIAP3 c.-11+996C>G Uncertain significance ★ ⚠ same type
BAIAP3 c.-6C>T Uncertain significance ★ ⚠ same type
BAIAP3 p.Ala1007Gly 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/baiap3-p-ser695phe (accessed [today's date]).

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