Is PHF2 p.Ala25Val (c.74C>T) pathogenic?

PHF2 p.Ala25Val (c.74C>T) is classified Uncertain significance in PHF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: ambiguous (0.3493); No allele count reported in gnomAD v4.1 (AN 1,280,500).

How common is PHF2 p.Ala25Val (c.74C>T) in the general population?

PHF2 p.Ala25Val (c.74C>T) is no allele count reported in gnomAD v4.1 (AN 1,280,500) (gnomAD).

What do computational predictors say about PHF2 p.Ala25Val (c.74C>T)?

AlphaMissense predicts ambiguous (score 0.3493) — an in-silico prediction, not a clinical call.

PHF2 p.Ala25Val

c.74C>T · VCV3931532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3493 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,280,500)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3493	ambiguous
REVEL	0.073	moderately benign-leaning
SaProt	LLR -5.74	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -2.3, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 83 kb · p 8.8e-22 · regional, not allelic
Overall
CADD	21.9	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

No allele count reported in gnomAD v4.1 (AN 1,280,500). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHF2
Protein: p.Ala25Val
Coding: c.74C>T
MANE Select: NM_005392
Type: single nucleotide variant
Location: chr9:93576847 (GRCh38)
Gene constraint: LOEUF 0.329 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.14 · 9 PDB
Residue 25: a turn

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-ala25val (accessed [today's date]).

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