Is SDAD1 p.Pro14Ser (c.40C>T) pathogenic?

SDAD1 p.Pro14Ser (c.40C>T) is classified Uncertain significance in SDAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: ambiguous (0.5282); Very rare (popmax 0.00167%, amr).

How common is SDAD1 p.Pro14Ser (c.40C>T) in the general population?

SDAD1 p.Pro14Ser (c.40C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about SDAD1 p.Pro14Ser (c.40C>T)?

AlphaMissense predicts ambiguous (score 0.5282) — an in-silico prediction, not a clinical call.

SDAD1 p.Pro14Ser

c.40C>T · VCV4581491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5282 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.5282	ambiguous
REVEL	0.585	indeterminate
SaProt	LLR -12.23	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 40 kb · p 0.46 · regional, not allelic
Overall
CADD	29.2	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 0.00167% Admixed American · 1/60,024 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,614,154 alleles · very rare exomes 10/1,461,852 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,253
Admixed Americangrpmax	0.00167%	60,024
European (non-Finnish)	0.000593%	168,576

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SDAD1
Protein: p.Pro14Ser
Coding: c.40C>T
MANE Select: NM_018115
Type: single nucleotide variant
Location: chr4:75990802 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.64 · 7 PDB
Residue 14: an α-helix

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

Similar variants

SDAD1 p.Pro14Leu Uncertain significance ★ ⚠ same residue
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

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-pro14ser (accessed [today's date]).

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