Is BTD p.Ser414Cys (c.1241C>G) pathogenic?

BTD p.Ser414Cys (c.1241C>G) is classified Uncertain significance in BTD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely benign (0.2509); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BTD p.Ser414Cys (c.1241C>G)?

BTD p.Ser414Cys (c.1241C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BTD p.Ser414Cys (c.1241C>G) in the general population?

BTD p.Ser414Cys (c.1241C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BTD p.Ser414Cys (c.1241C>G)?

AlphaMissense predicts likely benign (score 0.2509) — an in-silico prediction, not a clinical call.

BTD p.Ser414Cys

c.1241C>G · VCV3482848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2509 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2509	likely benign
REVEL	0.395	indeterminate
SaProt	LLR -10.66	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 10 kb · p 0.35 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S434C vs ClinVar S414C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.84e-05% 1/1,461,884 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: BTD
Protein: p.Ser414Cys
Coding: c.1241C>G
MANE Select: NM_001370658
Type: single nucleotide variant
Location: chr3:15645157 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.77

Full BTD 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

BTD p.Ser414= Likely benign ★ same residue
BTD p.Gly94Val Pathogenic/Likely pathogenic ★★ same condition
BTD p.His465Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
BTD p.Asn152Ser Uncertain significance ★★ ⚠ same condition
BTD p.Asp304Glu Uncertain significance ★★ ⚠ same condition
BTD p.Asp348Ala Uncertain significance ★★ ⚠ same condition
BTD p.Cys351Arg Uncertain significance ★★ ⚠ same condition
BTD p.Gln68His 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/btd-p-ser414cys (accessed [today's date]).

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