Is PHRF1 p.Ser48Ile (c.143G>T) pathogenic?

PHRF1 p.Ser48Ile (c.143G>T) is classified Uncertain significance in PHRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.1893); No allele count reported in gnomAD v4.1 (AN 1,608,430).

How common is PHRF1 p.Ser48Ile (c.143G>T) in the general population?

PHRF1 p.Ser48Ile (c.143G>T) is no allele count reported in gnomAD v4.1 (AN 1,608,430) (gnomAD).

What do computational predictors say about PHRF1 p.Ser48Ile (c.143G>T)?

AlphaMissense predicts likely benign (score 0.1893) — an in-silico prediction, not a clinical call.

PHRF1 p.Ser48Ile

c.143G>T · VCV4567696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1893 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,430)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1893	likely benign
REVEL	0.368	indeterminate
SaProt	LLR -9.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 30 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	20.9	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

No allele count reported in gnomAD v4.1 (AN 1,608,430). 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: PHRF1
Protein: p.Ser48Ile
Coding: c.143G>T
MANE Select: NM_001286581
Type: single nucleotide variant
Location: chr11:582010 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.11
Residue 48: the 'disordered' region

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-ser48ile (accessed [today's date]).

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