Is PHRF1 p.Ala239Val (c.716C>T) pathogenic?

PHRF1 p.Ala239Val (c.716C>T) is classified Uncertain significance in PHRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.0933); Very rare (popmax 0.00333%, amr).

How common is PHRF1 p.Ala239Val (c.716C>T) in the general population?

PHRF1 p.Ala239Val (c.716C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about PHRF1 p.Ala239Val (c.716C>T)?

AlphaMissense predicts likely benign (score 0.0933) — an in-silico prediction, not a clinical call.

PHRF1 p.Ala239Val

c.716C>T · VCV3306298

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0933	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -2.2, phastCons 0.002
Regional constraint	o/e 1.10	unconstrained · MANE · 30 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	17.52	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 0.00333% Admixed American · 2/59,986 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00149% 24/1,613,390 alleles · very rare exomes 20/1,461,236 · genomes 4/152,154 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,993
European (non-Finnish)	0.00178%	56,172
Remaining individualsnot grpmax-eligible	0.0016%	62,442

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: PHRF1
Protein: p.Ala239Val
Coding: c.716C>T
MANE Select: NM_001286581
Type: single nucleotide variant
Location: chr11:597018 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.11

Full PHRF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PHRF1 p.Ala1355= Benign ★★ same type
PHRF1 p.Gly1209Arg Benign ★★ same type
PHRF1 p.Ser1168Leu Benign ★★ same type
PHRF1 p.Ser1457Gly Likely benign ★★ same type
PHRF1 p.Thr959= Likely benign ★★ same type
PHRF1 p.Ala114Ser Uncertain significance ★ ⚠ same type
PHRF1 p.Ala114Val Uncertain significance ★ ⚠ same type
PHRF1 p.Ala1197Ser Uncertain significance ★ ⚠ 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/phrf1-p-ala239val (accessed [today's date]).

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