Is SSB p.Pro96His (c.287C>A) pathogenic?

SSB p.Pro96His (c.287C>A) is classified Uncertain significance in SSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely pathogenic (0.8207); Absent from gnomAD v4.1.

How common is SSB p.Pro96His (c.287C>A) in the general population?

SSB p.Pro96His (c.287C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SSB p.Pro96His (c.287C>A)?

AlphaMissense predicts likely pathogenic (score 0.8207) — an in-silico prediction, not a clinical call.

SSB p.Pro96His

c.287C>A · VCV3962390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8207 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8207	likely pathogenic
REVEL	0.431	indeterminate
SaProt	LLR -14.20	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 11 kb · p 3.7e-12 · regional, not allelic
Overall
CADD	26.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SSB
Protein: p.Pro96His
Coding: c.287C>A
MANE Select: NM_003142
Type: single nucleotide variant
Location: chr2:169805781 (GRCh38)
Gene constraint: LOEUF 0.405 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 11 PDB
Residue 96: the hth la-type rna-binding domain; an α-helix

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

Similar variants

SSB p.Ala122Glu Uncertain significance ★ ⚠ same type
SSB p.Ala12Val Uncertain significance ★ ⚠ same type
SSB p.Ala221Gly Uncertain significance ★ ⚠ same type
SSB p.Ala289Thr Uncertain significance ★ ⚠ same type
SSB p.Ala405Pro Uncertain significance ★ ⚠ same type
SSB p.Arg111Lys Uncertain significance ★ ⚠ same type
SSB p.Arg334Cys Uncertain significance ★ ⚠ same type
SSB p.Arg334Gly 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/ssb-p-pro96his (accessed [today's date]).

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