Is BMPER p.Phe401Ser (c.1202T>C) pathogenic?

BMPER p.Phe401Ser (c.1202T>C) is classified Uncertain significance in BMPER (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-07-21). AlphaMissense: likely pathogenic (0.976); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with BMPER p.Phe401Ser (c.1202T>C)?

BMPER p.Phe401Ser (c.1202T>C) is associated with Inborn genetic diseases (ClinVar).

How common is BMPER p.Phe401Ser (c.1202T>C) in the general population?

BMPER p.Phe401Ser (c.1202T>C) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about BMPER p.Phe401Ser (c.1202T>C)?

AlphaMissense predicts likely pathogenic (score 0.976) — an in-silico prediction, not a clinical call.

BMPER p.Phe401Ser

c.1202T>C · rs775555876 · VCV1706313

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.976 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.976	likely pathogenic
REVEL	0.73	pathogenic-leaning
SaProt	LLR -14.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/60,020 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00062% 10/1,614,170 alleles · ultra-rare exomes 10/1,461,894 · genomes 0/152,276 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,669
African / African-American	0.00133%	75,044

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: BMPER
Protein: p.Phe401Ser
Coding: c.1202T>C
MANE Select: NM_001365308
dbSNP: rs775555876
Type: single nucleotide variant
Location: chr7:34078980 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 401: the vwfd domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMPER p.Ala39Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Arg16Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Arg332His Uncertain significance ★★ ⚠ same condition
BMPER p.Arg410His Uncertain significance ★★ ⚠ same condition
BMPER p.Arg505His Uncertain significance ★★ same condition
BMPER p.Arg558Gln Uncertain significance ★★ ⚠ same condition
BMPER p.Arg582Gln Uncertain significance ★★ ⚠ same condition
BMPER p.Asn65Lys Uncertain significance ★★ ⚠ 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/bmper-p-phe401ser (accessed [today's date]).

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