Is AATF p.Ala198Pro (c.592G>C) pathogenic?

AATF p.Ala198Pro (c.592G>C) is classified Uncertain significance in AATF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.091); Very rare (popmax 0.00333%, amr).

How common is AATF p.Ala198Pro (c.592G>C) in the general population?

AATF p.Ala198Pro (c.592G>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about AATF p.Ala198Pro (c.592G>C)?

AlphaMissense predicts likely benign (score 0.091) — an in-silico prediction, not a clinical call.

AATF p.Ala198Pro

c.592G>C · VCV4225743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.091	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -7.00	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 0.98	GERP 1.3, phastCons 0.001
Regional constraint	o/e 0.93	unconstrained · MANE · 108 kb · p 0.074 · regional, not allelic
Overall
CADD	12.89	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,614,098 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,004
African / African-American	0.00133%	74,920

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: AATF
Protein: p.Ala198Pro
Coding: c.592G>C
MANE Select: NM_012138
Type: single nucleotide variant
Location: chr17:36953194 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.74 · 3 PDB
Residue 198: the 'disordered' region

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

Similar variants

AATF p.Ala198Thr Uncertain significance ★ ⚠ same residue
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
AATF p.Arg287Lys 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-ala198pro (accessed [today's date]).

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