Is SPTB p.Ser1968Phe (c.5903C>T) pathogenic?

SPTB p.Ser1968Phe (c.5903C>T) is classified Uncertain significance in SPTB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-11). AlphaMissense: likely benign (0.174); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with SPTB p.Ser1968Phe (c.5903C>T)?

SPTB p.Ser1968Phe (c.5903C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SPTB p.Ser1968Phe (c.5903C>T) in the general population?

SPTB p.Ser1968Phe (c.5903C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about SPTB p.Ser1968Phe (c.5903C>T)?

AlphaMissense predicts likely benign (score 0.174) — an in-silico prediction, not a clinical call.

SPTB p.Ser1968Phe

c.5903C>T · VCV4865079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.174 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.174	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -10.81	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 46 kb · p 0.0029 · regional, not allelic
Overall
CADD	24.1	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 0.0011% South Asian · 1/91,084 alleles

Overall 6.2e-05% 1/1,614,088 alleles · very rare exomes 1/1,461,726 · genomes 0/152,362 · joint denominator

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: SPTB
Protein: p.Ser1968Phe
Coding: c.5903C>T
MANE Select: NM_001355436
Type: single nucleotide variant
Location: chr14:64769624 (GRCh38)
Gene constraint: LOEUF 0.228 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.55 · 6 PDB
Residue 1968: an α-helix

Full SPTB 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

SPTB p.Ser1968fs Pathogenic ★★ same residue
SPTB p.Ala1152Gly Uncertain significance ★★ ⚠ same condition
SPTB p.Ala1180Thr Uncertain significance ★★ ⚠ same condition
SPTB p.Ala1632Val Uncertain significance ★★ ⚠ same condition
SPTB p.Ala1741Val Uncertain significance ★★ ⚠ same condition
SPTB p.Ala1760Val Uncertain significance ★★ ⚠ same condition
SPTB p.Ala1795Thr Uncertain significance ★★ ⚠ same condition
SPTB p.Ala1903Val 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/sptb-p-ser1968phe (accessed [today's date]).

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