Is PHF12 p.Pro47Ser (c.139C>T) pathogenic?

PHF12 p.Pro47Ser (c.139C>T) is classified Uncertain significance in PHF12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.0856); Very rare (popmax 0.00356%, nfe).

How common is PHF12 p.Pro47Ser (c.139C>T) in the general population?

PHF12 p.Pro47Ser (c.139C>T) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about PHF12 p.Pro47Ser (c.139C>T)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

PHF12 p.Pro47Ser

c.139C>T · rs377511362 · VCV2313848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.4	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 809 bp · p 0.68 · regional, not allelic
Overall
CADD	21.5	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 0.00356% European (non-Finnish) · 42/1,180,008 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00279% 45/1,613,646 alleles · very rare exomes 42/1,461,574 · genomes 3/152,072 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00356%	28,095
Remaining individualsnot grpmax-eligible	0.0032%	31,242
African / African-American	0.00134%	74,868

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: PHF12
Protein: p.Pro47Ser
Coding: c.139C>T
MANE Select: NM_001033561
dbSNP: rs377511362
Type: single nucleotide variant
Location: chr17:28950174 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.98 · 6 PDB
Residue 47: the 'disordered' region

Full PHF12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PHF12 p.Leu324Met Uncertain significance ★★ ⚠ same type
PHF12 p.Ala152Ser Uncertain significance ★ ⚠ same type
PHF12 p.Ala171Val Uncertain significance ★ ⚠ same type
PHF12 p.Ala196Thr Uncertain significance ★ ⚠ same type
PHF12 p.Ala36Thr Uncertain significance ★ ⚠ same type
PHF12 p.Ala395Pro Uncertain significance ★ ⚠ same type
PHF12 p.Ala398Ser Uncertain significance ★ ⚠ same type
PHF12 p.Ala483Val 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/phf12-p-pro47ser (accessed [today's date]).

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