Is AATF p.Ser214Arg (c.642T>A) pathogenic?

AATF p.Ser214Arg (c.642T>A) is classified Uncertain significance in AATF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.1702); Ultra-rare (popmax 0.0379%, eas).

How common is AATF p.Ser214Arg (c.642T>A) in the general population?

AATF p.Ser214Arg (c.642T>A) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

What do computational predictors say about AATF p.Ser214Arg (c.642T>A)?

AlphaMissense predicts likely benign (score 0.1702) — an in-silico prediction, not a clinical call.

AATF p.Ser214Arg

c.642T>A · rs765216865 · VCV3144679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1702 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1702	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.55	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 -1.1	GERP -4.8
Regional constraint	o/e 0.93	unconstrained · MANE · 108 kb · p 0.074 · regional, not allelic
Overall
CADD	1.355	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 0.0379% East Asian · 17/44,894 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00112% 18/1,614,040 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,641
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Ser214Arg
Coding: c.642T>A
MANE Select: NM_012138
dbSNP: rs765216865
Type: single nucleotide variant
Location: chr17:36953244 (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-ser214arg (accessed [today's date]).

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