Is ATF7IP p.Asn529Ser (c.1586A>G) pathogenic?

ATF7IP p.Asn529Ser (c.1586A>G) is classified Benign in ATF7IP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-26). AlphaMissense: likely benign (0.0503); Low-frequency (popmax 1.37%, sas).

How common is ATF7IP p.Asn529Ser (c.1586A>G) in the general population?

ATF7IP p.Asn529Ser (c.1586A>G) is low-frequency (popmax 1.37%, sas) (gnomAD).

What do computational predictors say about ATF7IP p.Asn529Ser (c.1586A>G)?

AlphaMissense predicts likely benign (score 0.0503) — an in-silico prediction, not a clinical call.

ATF7IP p.Asn529Ser

c.1586A>G · rs145246872 · VCV749401

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0503 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0503	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -5.74	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 -0.5	GERP -2
Regional constraint	o/e 1.01	unconstrained · MANE · 11 kb · p 0.91 · regional, not allelic
Overall
CADD	3.337	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 1.37% South Asian · 1,225/89,378 alleles

Filtering AF 1.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.28%

Overall 0.0923% 1,468/1,591,008 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.37%	73
Ashkenazi Jewishnot grpmax-eligible	0.48%	208
Remaining individualsnot grpmax-eligible	0.11%	908
African / African-American	0.0067%	14,929
East Asian	0.00452%	22,144
European (non-Finnish)	0.00232%	43,025

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.Asn529Ser
Coding: c.1586A>G
MANE Select: NM_018179
dbSNP: rs145246872
Type: single nucleotide variant
Location: chr12:14434364 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.39 · 1 PDB
Residue 529: 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-asn529ser (accessed [today's date]).

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