Is SETD7 p.Pro210Leu (c.629C>T) pathogenic?

SETD7 p.Pro210Leu (c.629C>T) is classified Uncertain significance in SETD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely benign (0.2233); Very rare (popmax 0.00382%, nfe).

How common is SETD7 p.Pro210Leu (c.629C>T) in the general population?

SETD7 p.Pro210Leu (c.629C>T) is very rare (popmax 0.00382%, nfe) (gnomAD).

What do computational predictors say about SETD7 p.Pro210Leu (c.629C>T)?

AlphaMissense predicts likely benign (score 0.2233) — an in-silico prediction, not a clinical call.

SETD7 p.Pro210Leu

c.629C>T · rs377582482 · VCV2216418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2233 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00382%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2233	likely benign
REVEL	0.54	indeterminate
SaProt	LLR -11.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 38 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	24.9	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 0.00382% European (non-Finnish) · 45/1,178,086 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00285% 46/1,611,728 alleles · very rare exomes 41/1,459,598 · genomes 5/152,130 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00382%	26,180
Remaining individualsnot grpmax-eligible	0.0016%	62,430

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.Pro210Leu
Coding: c.629C>T
MANE Select: NM_030648
dbSNP: rs377582482
Type: single nucleotide variant
Location: chr4:139523369 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 94.51 · 32 PDB
Residue 210: an α-helix

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-pro210leu (accessed [today's date]).

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