Is ATF7IP p.Ile911Val (c.2731A>G) pathogenic?

ATF7IP p.Ile911Val (c.2731A>G) is classified Uncertain significance in ATF7IP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: ambiguous (0.3925); Very rare (popmax 0.00133%, afr).

How common is ATF7IP p.Ile911Val (c.2731A>G) in the general population?

ATF7IP p.Ile911Val (c.2731A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ATF7IP p.Ile911Val (c.2731A>G)?

AlphaMissense predicts ambiguous (score 0.3925) — an in-silico prediction, not a clinical call.

ATF7IP p.Ile911Val

c.2731A>G · rs1322444728 · VCV3130833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3925 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3925	ambiguous
REVEL	0.114	moderately benign-leaning
SaProt	LLR -6.19	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 37 kb · p 0.12 · regional, not allelic
Overall
CADD	21.9	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

Grpmax group 0.00133% African / African-American · 1/74,908 alleles

Overall 0.000657% 1/152,134 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.Ile911Val
Coding: c.2731A>G
MANE Select: NM_018179
dbSNP: rs1322444728
Type: single nucleotide variant
Location: chr12:14461067 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.39 · 1 PDB

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-ile911val (accessed [today's date]).

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