Is ATAD5 p.Ser1589Phe (c.4766C>T) pathogenic?

ATAD5 p.Ser1589Phe (c.4766C>T) is classified Likely benign in ATAD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely benign (0.0757); Ultra-rare (popmax 0.0165%, mid).

How common is ATAD5 p.Ser1589Phe (c.4766C>T) in the general population?

ATAD5 p.Ser1589Phe (c.4766C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ATAD5 p.Ser1589Phe (c.4766C>T)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

ATAD5 p.Ser1589Phe

c.4766C>T · VCV3959415

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.019	GERP -3.5
Regional constraint	o/e 0.81	unconstrained · MANE · 7,569 bp · p 3.5e-05 · regional, not allelic
Overall
CADD	0.114	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000137% 2/1,461,624 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	8.48e-05%	1,179,935

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: ATAD5
Protein: p.Ser1589Phe
Coding: c.4766C>T
MANE Select: NM_024857
Type: single nucleotide variant
Location: chr17:30893619 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.76 · 4 PDB

Full ATAD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATAD5 c.4013-8G>A Benign ★★ same type
ATAD5 p.Asp826= Likely benign ★★ same type
ATAD5 p.Ala1326Thr Uncertain significance ★ ⚠ same type
ATAD5 p.Ala1459Thr Uncertain significance ★ ⚠ same type
ATAD5 p.Ala1539Pro Uncertain significance ★ ⚠ same type
ATAD5 p.Ala1711Val Uncertain significance ★ ⚠ same type
ATAD5 p.Ala326Val Uncertain significance ★ ⚠ same type
ATAD5 p.Ala414Thr 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/atad5-p-ser1589phe (accessed [today's date]).

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