Is ATF7IP p.Ser546Pro (c.1636T>C) pathogenic?

ATF7IP p.Ser546Pro (c.1636T>C) is classified Uncertain significance in ATF7IP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.1002); Absent from gnomAD v4.1.

How common is ATF7IP p.Ser546Pro (c.1636T>C) in the general population?

ATF7IP p.Ser546Pro (c.1636T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATF7IP p.Ser546Pro (c.1636T>C)?

AlphaMissense predicts likely benign (score 0.1002) — an in-silico prediction, not a clinical call.

ATF7IP p.Ser546Pro

c.1636T>C · VCV3442622

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1002 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,569,830)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1002	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.90	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 3.1	GERP -0.32, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 11 kb · p 0.91 · regional, not allelic
Overall
CADD	19.46	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

No allele count reported in gnomAD v4.1 (AN 1,569,830). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATF7IP
Protein: p.Ser546Pro
Coding: c.1636T>C
MANE Select: NM_018179
Type: single nucleotide variant
Location: chr12:14434414 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.39 · 1 PDB
Residue 546: 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-ser546pro (accessed [today's date]).

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