Is ZNF207 p.Pro477Ser (c.1429C>T) pathogenic?

ZNF207 p.Pro477Ser (c.1429C>T) is classified Uncertain significance in ZNF207 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely benign (0.1001); Very rare (popmax 0.0018%, amr).

How common is ZNF207 p.Pro477Ser (c.1429C>T) in the general population?

ZNF207 p.Pro477Ser (c.1429C>T) is very rare (popmax 0.0018%, amr) (gnomAD).

What do computational predictors say about ZNF207 p.Pro477Ser (c.1429C>T)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

ZNF207 p.Pro477Ser

c.1429C>T · VCV3985812

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0018%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -12.54	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,033 bp · p 0.00089 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P461S vs ClinVar P477S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0018% Admixed American · 1/55,600 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000502% 8/1,593,112 alleles · very rare exomes 6/1,440,916 · genomes 2/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0018%	55,600
African / African-American	0.00135%	73,892
European (non-Finnish)	0.000512%	195,162

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: ZNF207
Protein: p.Pro477Ser
Coding: c.1429C>T
MANE Select: NM_001098507
Type: single nucleotide variant
Location: chr17:32369703 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 61.30
Residue 461 UniProt numbering: the 'disordered' region

Full ZNF207 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ZNF207 p.Ala254Glu Uncertain significance ★ ⚠ same type
ZNF207 p.Ala356Gly Uncertain significance ★ ⚠ same type
ZNF207 p.Arg478Gln Uncertain significance ★ ⚠ same type
ZNF207 p.Asn199Lys Uncertain significance ★ same type
ZNF207 p.Asn401Ser Uncertain significance ★ ⚠ same type
ZNF207 p.Asp111Gly Uncertain significance ★ ⚠ same type
ZNF207 p.Asp120Asn Uncertain significance ★ ⚠ same type
ZNF207 p.Gln309Leu 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/znf207-p-pro477ser (accessed [today's date]).

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