Is ATAD3A p.Ser48Arg (c.144C>G) pathogenic?

ATAD3A p.Ser48Arg (c.144C>G) is classified Uncertain significance in ATAD3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely pathogenic (0.9109); Very rare (popmax 0.00401%, sas); Associated with Inborn genetic diseases.

What condition is associated with ATAD3A p.Ser48Arg (c.144C>G)?

ATAD3A p.Ser48Arg (c.144C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ATAD3A p.Ser48Arg (c.144C>G) in the general population?

ATAD3A p.Ser48Arg (c.144C>G) is very rare (popmax 0.00401%, sas) (gnomAD).

What do computational predictors say about ATAD3A p.Ser48Arg (c.144C>G)?

AlphaMissense predicts likely pathogenic (score 0.9109) — an in-silico prediction, not a clinical call.

ATAD3A p.Ser48Arg

c.144C>G · rs2100637773 · VCV3130682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9109	likely pathogenic
REVEL	0.507	indeterminate
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 5,138 bp · p 0.00048 · regional, not allelic
Overall
CADD	25.7	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 0.00401% South Asian · 1/24,920 alleles

Overall 0.000667% 1/150,016 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: ATAD3A
Protein: p.Ser48Arg
Coding: c.144C>G
MANE Select: NM_001170535
dbSNP: rs2100637773
Type: single nucleotide variant
Location: chr1:1512412 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 48: the 'disordered' region; the 'required for interaction with the inner surface of the mitochondrial outer membrane' region

Full ATAD3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATAD3A p.Ala62Val Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg138Trp Uncertain significance ★★ same condition
ATAD3A p.Arg188Gln Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg208Cys Uncertain significance ★★ same condition
ATAD3A p.Arg212Cys Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg273Cys Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg327Gln Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg327Leu Uncertain significance ★★ ⚠ same condition

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/atad3a-p-ser48arg (accessed [today's date]).

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