Is PHF2 p.Thr124= (c.372C>T) pathogenic?

PHF2 p.Thr124= (c.372C>T) is classified Benign in PHF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-06-13). Common (popmax 17.6%, nfe) — too common for a highly-penetrant pathogenic allele.

PHF2 p.Thr124=

Q: How common is PHF2 p.Thr124= (c.372C>T) in the general population?

PHF2 p.Thr124= (c.372C>T) is common (popmax 17.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.372C>T · rs9695734 · VCV1262733

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 17.6%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	0.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.6% European (non-Finnish) · 207,223/1,179,350 alleles

Filtering AF 17.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.5%

Overall 16.1% 259,008/1,612,274 alleles · common exomes 237,600/1,459,986 · genomes 21,408/152,288 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	18.4%	5
European (non-Finnish)grpmax	17.6%	6
Remaining individualsnot grpmax-eligible	16.2%	6
Middle Eastern	16%	6
African / African-American	12.5%	8
Finnishnot grpmax-eligible	12%	8
South Asian	11.3%	9
Admixed American	8.88%	11
Amishnot grpmax-eligible	8.11%	12
East Asian	6.03%	17

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PHF2
Protein: p.Thr124=
Coding: c.372C>T
MANE Select: NM_005392
dbSNP: rs9695734
Type: single nucleotide variant
Location: chr9:93645701 (GRCh38)
Gene constraint: LOEUF 0.329 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.14 · 9 PDB

Full PHF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PHF2 c.299+7T>A Benign ★★ same type
PHF2 c.789+10G>A Benign/Likely benign ★★ same type
PHF2 p.Asp103= Benign ★★ same type
PHF2 p.Leu645= Benign/Likely benign ★★ same type
PHF2 p.Pro786= Benign ★★ same type
PHF2 p.Pro988= Benign ★★ same type
PHF2 p.Ser725= Benign ★★ same type
PHF2 p.Ser738= Benign ★★ 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/phf2-p-thr124 (accessed [today's date]).

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