Is AATF p.Leu7Pro (c.20T>C) pathogenic?

AATF p.Leu7Pro (c.20T>C) is classified Uncertain significance in AATF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: likely pathogenic (0.6005); Ultra-rare (popmax 0.0479%, eas).

How common is AATF p.Leu7Pro (c.20T>C) in the general population?

AATF p.Leu7Pro (c.20T>C) is ultra-rare (popmax 0.0479%, eas) (gnomAD).

What do computational predictors say about AATF p.Leu7Pro (c.20T>C)?

AlphaMissense predicts likely pathogenic (score 0.6005) — an in-silico prediction, not a clinical call.

AATF p.Leu7Pro

c.20T>C · rs369810199 · VCV2518270

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6005 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0479%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6005	likely pathogenic
REVEL	0.282	benign-leaning
SaProt	LLR -11.68	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 108 kb · p 0.074 · regional, not allelic
Overall
CADD	23.2	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 0.0479% East Asian · 21/43,838 alleles

Filtering AF 0.032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.027%

Overall 0.00177% 28/1,584,294 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0479%	2,088
Remaining individualsnot grpmax-eligible	0.0065%	15,373
South Asian	0.00116%	86,448
European (non-Finnish)	0.000171%	583,461

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.Leu7Pro
Coding: c.20T>C
MANE Select: NM_012138
dbSNP: rs369810199
Type: single nucleotide variant
Location: chr17:36949145 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.74 · 3 PDB

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-leu7pro (accessed [today's date]).

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