Is ATAD3B p.Ser162Phe (c.485C>T) pathogenic?

ATAD3B p.Ser162Phe (c.485C>T) is classified Uncertain significance in ATAD3B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-23). AlphaMissense: ambiguous (0.3899); Very rare (popmax 0.00367%, nfe).

How common is ATAD3B p.Ser162Phe (c.485C>T) in the general population?

ATAD3B p.Ser162Phe (c.485C>T) is very rare (popmax 0.00367%, nfe) (gnomAD).

What do computational predictors say about ATAD3B p.Ser162Phe (c.485C>T)?

AlphaMissense predicts ambiguous (score 0.3899) — an in-silico prediction, not a clinical call.

ATAD3B p.Ser162Phe

c.485C>T · VCV3441266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3899 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00367%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3899	ambiguous
REVEL	0.24	benign-leaning
SaProt	LLR -7.90	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 10 kb · p 0.00025 · regional, not allelic
Overall
CADD	25.2	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 0.00367% European (non-Finnish) · 43/1,171,856 alleles

Filtering AF 0.00277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.0027% 43/1,593,302 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.Ser162Phe
Coding: c.485C>T
MANE Select: NM_031921
Type: single nucleotide variant
Location: chr1:1480907 (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 p.Ser162Thr Uncertain significance ★ ⚠ same residue
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

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-ser162phe (accessed [today's date]).

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