Is PHF2 p.Val6Met (c.16G>A) pathogenic?

PHF2 p.Val6Met (c.16G>A) is classified Uncertain significance in PHF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-28). AlphaMissense: likely pathogenic (0.9849); Very rare (popmax 7.83e-05%).

How common is PHF2 p.Val6Met (c.16G>A) in the general population?

PHF2 p.Val6Met (c.16G>A) is very rare (popmax 7.83e-05%) (gnomAD).

What do computational predictors say about PHF2 p.Val6Met (c.16G>A)?

AlphaMissense predicts likely pathogenic (score 0.9849) — an in-silico prediction, not a clinical call.

PHF2 p.Val6Met

c.16G>A · rs1359388349 · VCV2621720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9849 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.83e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9849	likely pathogenic · top 9% in PHF2
REVEL	0.196	benign-leaning
SaProt	LLR -9.70	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 83 kb · p 8.8e-22 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 7.83e-05%

Overall 7.83e-05% 1/1,276,924 alleles · very rare exomes 1/1,131,740 · genomes 0/145,184 · joint denominator

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.Val6Met
Coding: c.16G>A
MANE Select: NM_005392
dbSNP: rs1359388349
Type: single nucleotide variant
Location: chr9:93576789 (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-val6met (accessed [today's date]).

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