Is ATF7IP p.Asp400Val (c.1199A>T) pathogenic?

ATF7IP p.Asp400Val (c.1199A>T) is classified Uncertain significance in ATF7IP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely benign (0.0888); Very rare (popmax 0.000256%, nfe).

How common is ATF7IP p.Asp400Val (c.1199A>T) in the general population?

ATF7IP p.Asp400Val (c.1199A>T) is very rare (popmax 0.000256%, nfe) (gnomAD).

What do computational predictors say about ATF7IP p.Asp400Val (c.1199A>T)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

ATF7IP p.Asp400Val

c.1199A>T · rs1941770114 · VCV3130821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000256%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.08	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 3	GERP -1.7, phastCons 0.97
Regional constraint	o/e 1.08	unconstrained · MANE · 1,014 bp · p 0.1 · regional, not allelic
Overall
CADD	18.83	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 0.000256% European (non-Finnish) · 3/1,173,176 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000209% 3/1,436,124 alleles · very rare

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: ATF7IP
Protein: p.Asp400Val
Coding: c.1199A>T
MANE Select: NM_018179
dbSNP: rs1941770114
Type: single nucleotide variant
Location: chr12:14425114 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.39 · 1 PDB
Residue 400: the 'disordered' region

Full ATF7IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATF7IP p.Ala1069Thr Benign ★★ same type
ATF7IP p.Leu149= Benign ★★ same type
ATF7IP p.Lys530Arg Benign ★★ ⚠ same type
ATF7IP p.Met573Ile Likely benign ★★ same type
ATF7IP p.Ser502Leu Likely benign ★★ same type
ATF7IP p.Ser734Asn Benign ★★ ⚠ same type
ATF7IP c.1559-2A>G Uncertain significance ★ same type
ATF7IP p.Ala1191Val 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/atf7ip-p-asp400val (accessed [today's date]).

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