Is ATAD3C p.Phe298Leu (c.892T>C) pathogenic?

ATAD3C p.Phe298Leu (c.892T>C) is classified Uncertain significance in ATAD3C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: likely pathogenic (0.8238); Ultra-rare (popmax 0.0147%, afr).

How common is ATAD3C p.Phe298Leu (c.892T>C) in the general population?

ATAD3C p.Phe298Leu (c.892T>C) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about ATAD3C p.Phe298Leu (c.892T>C)?

AlphaMissense predicts likely pathogenic (score 0.8238) — an in-silico prediction, not a clinical call.

ATAD3C p.Phe298Leu

c.892T>C · VCV3795545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8238 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8238	likely pathogenic · top 1% in ATAD3C
REVEL	0.453	indeterminate
SaProt	LLR -8.92	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 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.22 · regional, not allelic
Overall
CADD	23.9	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 0.0147% African / African-American · 11/74,992 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000806% 13/1,613,100 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,817
Remaining individualsnot grpmax-eligible	0.0016%	62,458
South Asian	0.0011%	90,936

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: ATAD3C
Protein: p.Phe298Leu
Coding: c.892T>C
MANE Select: NM_001039211
Type: single nucleotide variant
Location: chr1:1460829 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.72

Full ATAD3C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATAD3C p.Phe298Cys Uncertain significance ★ ⚠ same residue
ATAD3C p.Ala91Val Benign ★★ same type
ATAD3C p.His172Asn Likely benign ★★ same type
ATAD3C p.Ala101Thr Uncertain significance ★ ⚠ same type
ATAD3C p.Ala101Val Uncertain significance ★ ⚠ same type
ATAD3C p.Ala120Val Uncertain significance ★ ⚠ same type
ATAD3C p.Ala157Thr Uncertain significance ★ ⚠ same type
ATAD3C p.Ala224Thr 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/atad3c-p-phe298leu (accessed [today's date]).

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