Is ATAD3B p.Ser536Pro (c.1606T>C) pathogenic?

ATAD3B p.Ser536Pro (c.1606T>C) is classified Uncertain significance in ATAD3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: ambiguous (0.4647); Very rare (popmax 0.00366%, amr).

How common is ATAD3B p.Ser536Pro (c.1606T>C) in the general population?

ATAD3B p.Ser536Pro (c.1606T>C) is very rare (popmax 0.00366%, amr) (gnomAD).

What do computational predictors say about ATAD3B p.Ser536Pro (c.1606T>C)?

AlphaMissense predicts ambiguous (score 0.4647) — an in-silico prediction, not a clinical call.

ATAD3B p.Ser536Pro

c.1606T>C · VCV4643671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4647 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00366%, amr)

Computational evidence

Protein change
AlphaMissense	0.4647	ambiguous
REVEL	0.417	indeterminate
SaProt	LLR -10.70	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 0.5, phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 7,951 bp · p 7.5e-06 · regional, not allelic
Overall
CADD	22.4	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 0.00366% Admixed American · 2/54,652 alleles

Filtering AF 0.000607% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000227%

Overall 0.000139% 2/1,436,818 alleles · very rare

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: ATAD3B
Protein: p.Ser536Pro
Coding: c.1606T>C
MANE Select: NM_031921
Type: single nucleotide variant
Location: chr1:1490663 (GRCh38)
Gene constraint: LOEUF 1.152 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.69

Full ATAD3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATAD3B c.445-11C>G Benign ★★ same type
ATAD3B p.Ala71Ser Benign ★★ same type
ATAD3B p.Cys641= Benign ★★ same type
ATAD3B p.Phe274Tyr Benign/Likely benign ★★ same type
ATAD3B p.Pro639Ser Benign ★★ same type
ATAD3B p.Val259= Likely benign ★★ same type
ATAD3B c.1090-3C>T Uncertain significance ★ same type
ATAD3B c.325C>T 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/atad3b-p-ser536pro (accessed [today's date]).

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