Is ATAD3B p.Leu320Phe (c.958C>T) pathogenic?

ATAD3B p.Leu320Phe (c.958C>T) is classified Uncertain significance in ATAD3B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). AlphaMissense: likely benign (0.1787); Very rare (popmax 0.005%, amr).

How common is ATAD3B p.Leu320Phe (c.958C>T) in the general population?

ATAD3B p.Leu320Phe (c.958C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ATAD3B p.Leu320Phe (c.958C>T)?

AlphaMissense predicts likely benign (score 0.1787) — an in-silico prediction, not a clinical call.

ATAD3B p.Leu320Phe

c.958C>T · VCV3319921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1787	likely benign
REVEL	0.417	indeterminate
SaProt	LLR -8.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.86 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 4,459 bp · p 0.018 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.005% Admixed American · 3/59,954 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000682% 11/1,613,096 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,985
Remaining individualsnot grpmax-eligible	0.0016%	62,458
European (non-Finnish)	0.000593%	168,500

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.Leu320Phe
Coding: c.958C>T
MANE Select: NM_031921
Type: single nucleotide variant
Location: chr1:1485833 (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-leu320phe (accessed [today's date]).

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