Is ATAD2B p.Ser1304Phe (c.3911C>T) pathogenic?

ATAD2B p.Ser1304Phe (c.3911C>T) is classified Uncertain significance in ATAD2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: likely benign (0.0948); Ultra-rare (popmax 0.0143%, sas).

How common is ATAD2B p.Ser1304Phe (c.3911C>T) in the general population?

ATAD2B p.Ser1304Phe (c.3911C>T) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about ATAD2B p.Ser1304Phe (c.3911C>T)?

AlphaMissense predicts likely benign (score 0.0948) — an in-silico prediction, not a clinical call.

ATAD2B p.Ser1304Phe

c.3911C>T · rs372015732 · VCV2382903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0948 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0948	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 5,977 bp · p 0.0005 · regional, not allelic
Overall
CADD	23.6	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 0.0143% South Asian · 13/90,866 alleles

Filtering AF 0.00846% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00663%

Overall 0.00123% 18/1,460,826 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	6,990
East Asian	0.00223%	44,862
European (non-Finnish)	0.000339%	294,879

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: ATAD2B
Protein: p.Ser1304Phe
Coding: c.3911C>T
MANE Select: NM_017552
dbSNP: rs372015732
Type: single nucleotide variant
Location: chr2:23757585 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.47 · 6 PDB

Full ATAD2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATAD2B p.Leu68= Benign ★★ same type
ATAD2B p.Ala1111Pro Uncertain significance ★ ⚠ same type
ATAD2B p.Ala1232Pro Uncertain significance ★ ⚠ same type
ATAD2B p.Ala1375Val Uncertain significance ★ ⚠ same type
ATAD2B p.Ala31Ser Uncertain significance ★ ⚠ same type
ATAD2B p.Ala50Asp Uncertain significance ★ ⚠ same type
ATAD2B p.Ala692Val Uncertain significance ★ ⚠ same type
ATAD2B p.Ala975Thr 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/atad2b-p-ser1304phe (accessed [today's date]).

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