Is ATAD3C p.Phe234Leu (c.700T>C) pathogenic?

ATAD3C p.Phe234Leu (c.700T>C) is classified Uncertain significance in ATAD3C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.7825); Very rare (popmax 0.00526%, nfe).

How common is ATAD3C p.Phe234Leu (c.700T>C) in the general population?

ATAD3C p.Phe234Leu (c.700T>C) is very rare (popmax 0.00526%, nfe) (gnomAD).

What do computational predictors say about ATAD3C p.Phe234Leu (c.700T>C)?

AlphaMissense predicts likely pathogenic (score 0.7825) — an in-silico prediction, not a clinical call.

ATAD3C p.Phe234Leu

c.700T>C · VCV4161176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7825 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00526%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7825	likely pathogenic · top 1% in ATAD3C
REVEL	0.702	pathogenic-leaning
SaProt	LLR -10.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.22 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00526% European (non-Finnish) · 62/1,179,632 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.0039% 63/1,613,396 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00526%	19,026
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Phe234Leu
Coding: c.700T>C
MANE Select: NM_001039211
Type: single nucleotide variant
Location: chr1:1457139 (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.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
ATAD3C p.Ala240Thr 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-phe234leu (accessed [today's date]).

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