Is SDAD1 p.Pro366Ala (c.1096C>G) pathogenic?

SDAD1 p.Pro366Ala (c.1096C>G) is classified Uncertain significance in SDAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely pathogenic (0.8181); Absent from gnomAD v4.1.

How common is SDAD1 p.Pro366Ala (c.1096C>G) in the general population?

SDAD1 p.Pro366Ala (c.1096C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDAD1 p.Pro366Ala (c.1096C>G)?

AlphaMissense predicts likely pathogenic (score 0.8181) — an in-silico prediction, not a clinical call.

SDAD1 p.Pro366Ala

c.1096C>G · VCV3438598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8181 · 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	0.8181	likely pathogenic
REVEL	0.473	indeterminate
SaProt	LLR -12.76	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 40 kb · p 0.46 · regional, not allelic
Overall
CADD	27.3	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: SDAD1
Protein: p.Pro366Ala
Coding: c.1096C>G
MANE Select: NM_018115
Type: single nucleotide variant
Location: chr4:75965772 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.64 · 7 PDB

Full SDAD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SDAD1 p.Ala150Glu Uncertain significance ★ ⚠ same type
SDAD1 p.Ala150Thr Uncertain significance ★ ⚠ same type
SDAD1 p.Ala217Ser Uncertain significance ★ ⚠ same type
SDAD1 p.Ala243Thr Uncertain significance ★ ⚠ same type
SDAD1 p.Ala297Val Uncertain significance ★ same type
SDAD1 p.Ala64Val Uncertain significance ★ ⚠ same type
SDAD1 p.Arg127Cys Uncertain significance ★ ⚠ same type
SDAD1 p.Arg440Gln 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/sdad1-p-pro366ala (accessed [today's date]).

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