Is PHF2 p.Val192Ile (c.574G>A) pathogenic?

PHF2 p.Val192Ile (c.574G>A) is classified Uncertain significance in PHF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely benign (0.1073); Ultra-rare (popmax 0.0123%, eas).

How common is PHF2 p.Val192Ile (c.574G>A) in the general population?

PHF2 p.Val192Ile (c.574G>A) is ultra-rare (popmax 0.0123%, eas) (gnomAD).

What do computational predictors say about PHF2 p.Val192Ile (c.574G>A)?

AlphaMissense predicts likely benign (score 0.1073) — an in-silico prediction, not a clinical call.

PHF2 p.Val192Ile

c.574G>A · rs202018179 · VCV2261516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1073 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1073	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -7.76	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 6.1	GERP -2.4, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 83 kb · p 8.8e-22 · regional, not allelic
Overall
CADD	22.4	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 0.0123% East Asian · 5/40,616 alleles

Filtering AF 0.00482% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00416%

Overall 0.00491% 76/1,547,760 alleles · ultra-rare exomes 71/1,396,104 · genomes 5/151,656 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0123%	8,123
European (non-Finnish)	0.00568%	17,613
Finnishnot grpmax-eligible	0.00506%	19,754
Remaining individualsnot grpmax-eligible	0.00167%	59,874
African / African-American	0.00137%	72,910
South Asian	0.00119%	83,990

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.Val192Ile
Coding: c.574G>A
MANE Select: NM_005392
dbSNP: rs202018179
Type: single nucleotide variant
Location: chr9:93649184 (GRCh38)
Gene constraint: LOEUF 0.329 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.14 · 9 PDB
Residue 192: a β-strand

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-val192ile (accessed [today's date]).

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