Is AATF p.Ser99Cys (c.296C>G) pathogenic?

AATF p.Ser99Cys (c.296C>G) is classified Uncertain significance in AATF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0952); Absent from gnomAD v4.1.

How common is AATF p.Ser99Cys (c.296C>G) in the general population?

AATF p.Ser99Cys (c.296C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AATF p.Ser99Cys (c.296C>G)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

AATF p.Ser99Cys

c.296C>G · VCV4635754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -10.37	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 108 kb · p 0.074 · regional, not allelic
Overall
CADD	21.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AATF
Protein: p.Ser99Cys
Coding: c.296C>G
MANE Select: NM_012138
Type: single nucleotide variant
Location: chr17:36952898 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.74 · 3 PDB
Residue 99: the 'disordered' region

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

Similar variants

AATF p.Ala198Pro Uncertain significance ★ ⚠ same type
AATF p.Ala198Thr Uncertain significance ★ ⚠ same type
AATF p.Ala226Thr Uncertain significance ★ ⚠ same type
AATF p.Ala247Val Uncertain significance ★ ⚠ same type
AATF p.Ala2Gly Uncertain significance ★ ⚠ same type
AATF p.Ala314Val Uncertain significance ★ ⚠ same type
AATF p.Ala377Pro Uncertain significance ★ ⚠ same type
AATF p.Ala60Val 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/aatf-p-ser99cys (accessed [today's date]).

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