Is PHF2 p.Ser807= (c.2421C>T) pathogenic?

PHF2 p.Ser807= (c.2421C>T) is classified Likely benign in PHF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-20). Ultra-rare (popmax 0.0335%, mid).

How common is PHF2 p.Ser807= (c.2421C>T) in the general population?

PHF2 p.Ser807= (c.2421C>T) is ultra-rare (popmax 0.0335%, mid) (gnomAD).

PHF2 p.Ser807=

c.2421C>T · rs199537702 · VCV778436

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -2.3	GERP -3.8
Overall
CADD	16.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0335% Middle Eastern · 2/5,962 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00873%

Overall 0.0207% 334/1,610,854 alleles · ultra-rare exomes 303/1,458,564 · genomes 31/152,290 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.484%	207
Remaining individualsnot grpmax-eligible	0.0417%	2,397
Middle Easterngrpmax	0.0335%	2,981
African / African-American	0.0173%	5,770
South Asian	0.0165%	6,060
Admixed American	0.0117%	8,559
European (non-Finnish)	0.0109%	9,205

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.Ser807=
Coding: c.2421C>T
MANE Select: NM_005392
dbSNP: rs199537702
Type: single nucleotide variant
Location: chr9:93673657 (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-ser807 (accessed [today's date]).

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