Is ATF7IP2 p.Pro579Arg (c.1736C>G) pathogenic?

ATF7IP2 p.Pro579Arg (c.1736C>G) is classified Uncertain significance in ATF7IP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely pathogenic (0.9841); Absent from gnomAD v4.1.

How common is ATF7IP2 p.Pro579Arg (c.1736C>G) in the general population?

ATF7IP2 p.Pro579Arg (c.1736C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATF7IP2 p.Pro579Arg (c.1736C>G)?

AlphaMissense predicts likely pathogenic (score 0.9841) — an in-silico prediction, not a clinical call.

ATF7IP2 p.Pro579Arg

c.1736C>G · VCV3960195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9841 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9841	likely pathogenic · top 2% in ATF7IP2
REVEL	0.244	benign-leaning
SaProt	LLR -15.19	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 4	GERP 2.7, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 52 kb · p 1.1e-07 · regional, not allelic
Overall
CADD	26.9	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: ATF7IP2
Protein: p.Pro579Arg
Coding: c.1736C>G
MANE Select: NM_001393719
Type: single nucleotide variant
Location: chr16:10481936 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.88
Residue 579: the fibronectin type-iii domain

Full ATF7IP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATF7IP2 c.1095+1G>T Uncertain significance ★ same type
ATF7IP2 c.1482+1G>A Uncertain significance ★ same type
ATF7IP2 p.Ala134Ser Uncertain significance ★ ⚠ same type
ATF7IP2 p.Ala161Gly Uncertain significance ★ ⚠ same type
ATF7IP2 p.Ala161Thr Uncertain significance ★ ⚠ same type
ATF7IP2 p.Ala361Thr Uncertain significance ★ ⚠ same type
ATF7IP2 p.Ala366Val Uncertain significance ★ ⚠ same type
ATF7IP2 p.Ala540Ser 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/atf7ip2-p-pro579arg (accessed [today's date]).

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