Is PSD p.Pro94Ala (c.280C>G) pathogenic?

PSD p.Pro94Ala (c.280C>G) is classified Uncertain significance in PSD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.0511); Absent from gnomAD v4.1.

How common is PSD p.Pro94Ala (c.280C>G) in the general population?

PSD p.Pro94Ala (c.280C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PSD p.Pro94Ala (c.280C>G)?

AlphaMissense predicts likely benign (score 0.0511) — an in-silico prediction, not a clinical call.

PSD p.Pro94Ala

c.280C>G · VCV3310823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0511 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0511	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.91	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 6.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,529 bp · p 0.00029 · regional, not allelic
Overall
CADD	20.7	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

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: PSD
Protein: p.Pro94Ala
Coding: c.280C>G
MANE Select: NM_002779
Type: single nucleotide variant
Location: chr10:102416759 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 56.76
Residue 94: the 'disordered' region

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

Similar variants

PSD p.Gly336Ser Benign ★★ same type
PSD p.Leu659= Benign ★★ same type
PSD p.Ala1017Pro Uncertain significance ★ ⚠ same type
PSD p.Ala185Pro Uncertain significance ★ ⚠ same type
PSD p.Ala204Val Uncertain significance ★ ⚠ same type
PSD p.Ala260Val Uncertain significance ★ ⚠ same type
PSD p.Ala311Asp Uncertain significance ★ ⚠ same type
PSD p.Ala457Thr 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/psd-p-pro94ala (accessed [today's date]).

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