Is SSBP1 p.Pro5Ser (c.13C>T) pathogenic?

SSBP1 p.Pro5Ser (c.13C>T) is classified Uncertain significance in SSBP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely benign (0.1421); Rare (popmax 0.142%, afr); Associated with optic atrophy.

What condition is associated with SSBP1 p.Pro5Ser (c.13C>T)?

SSBP1 p.Pro5Ser (c.13C>T) is associated with optic atrophy (ClinVar).

How common is SSBP1 p.Pro5Ser (c.13C>T) in the general population?

SSBP1 p.Pro5Ser (c.13C>T) is rare (popmax 0.142%, afr) (gnomAD).

What do computational predictors say about SSBP1 p.Pro5Ser (c.13C>T)?

AlphaMissense predicts likely benign (score 0.1421) — an in-silico prediction, not a clinical call.

SSBP1 p.Pro5Ser

c.13C>T · VCV3250098

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1421 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.142%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

optic atrophy

Computational evidence

Protein change
AlphaMissense	0.1421	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -6.95	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	GERP 5.5, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 3,051 bp · p 0.036 · regional, not allelic
Overall
CADD	21.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.142% African / African-American · 106/74,498 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.00699% 112/1,601,660 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.142%	703
Middle Eastern	0.0166%	6,018
Admixed American	0.00344%	29,046
Remaining individualsnot grpmax-eligible	0.00161%	62,074
European (non-Finnish)	0.00017%	587,299

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: SSBP1
Protein: p.Pro5Ser
Coding: c.13C>T
MANE Select: NM_003143
Type: single nucleotide variant
Location: chr7:141739179 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 83.43 · 5 PDB

Full SSBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

optic atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SSBP1 p.Arg107Gln Pathogenic ★★ ⚠ same type
SSBP1 p.Val9Ile Uncertain significance ★★ ⚠ same type
SSBP1 p.Arg38Gln Pathogenic ★ same type
SSBP1 p.Gly40Val Likely pathogenic ★ same type
SSBP1 c.227-3T>A Uncertain significance ★ same type
SSBP1 c.24+3A>G Uncertain significance ★ same type
SSBP1 p.Arg32Cys Uncertain significance ★ same type
SSBP1 p.Arg32His 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/ssbp1-p-pro5ser (accessed [today's date]).

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