Is SETD7 p.Ile144Val (c.430A>G) pathogenic?

SETD7 p.Ile144Val (c.430A>G) is classified Uncertain significance in SETD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.074); Ultra-rare (popmax 0.0165%, mid).

How common is SETD7 p.Ile144Val (c.430A>G) in the general population?

SETD7 p.Ile144Val (c.430A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about SETD7 p.Ile144Val (c.430A>G)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

SETD7 p.Ile144Val

c.430A>G · VCV4582718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.36	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 4.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 38 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	18.46	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

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000124% 2/1,614,096 alleles · ultra-rare exomes 2/1,461,782 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	8.47e-05%	1,179,999

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: SETD7
Protein: p.Ile144Val
Coding: c.430A>G
MANE Select: NM_030648
Type: single nucleotide variant
Location: chr4:139529163 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 94.51 · 32 PDB
Residue 144: a β-strand

Full SETD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SETD7 p.Pro22= Benign ★★ same type
SETD7 p.Arg115Cys Uncertain significance ★ ⚠ same type
SETD7 p.Arg179Thr Uncertain significance ★ ⚠ same type
SETD7 p.Asp101His Uncertain significance ★ ⚠ same type
SETD7 p.Asp306Asn Uncertain significance ★ ⚠ same type
SETD7 p.Cys288Ser Uncertain significance ★ ⚠ same type
SETD7 p.Cys288Tyr Uncertain significance ★ ⚠ same type
SETD7 p.Cys303Ser 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/setd7-p-ile144val (accessed [today's date]).

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