Is PHRF1 p.Ser948Phe (c.2843C>T) pathogenic?

PHRF1 p.Ser948Phe (c.2843C>T) is classified Conflicting classifications of pathogenicity in PHRF1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-06-01). AlphaMissense: likely benign (0.1279); Ultra-rare (popmax 0.0339%, mid).

How common is PHRF1 p.Ser948Phe (c.2843C>T) in the general population?

PHRF1 p.Ser948Phe (c.2843C>T) is ultra-rare (popmax 0.0339%, mid) (gnomAD).

What do computational predictors say about PHRF1 p.Ser948Phe (c.2843C>T)?

AlphaMissense predicts likely benign (score 0.1279) — an in-silico prediction, not a clinical call.

PHRF1 p.Ser948Phe

c.2843C>T · rs200183606 · VCV2411337

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1279 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0339%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1279	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -8.22	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 2.9	phastCons 0.072
Regional constraint	o/e 1.10	unconstrained · MANE · 30 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	19.1	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 0.0339% Middle Eastern · 2/5,904 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00404%

Overall 0.0247% 397/1,609,304 alleles · ultra-rare exomes 353/1,457,096 · genomes 44/152,208 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.928%	108
Remaining individualsnot grpmax-eligible	0.0803%	1,246
Middle Easterngrpmax	0.0339%	2,952
European (non-Finnish)	0.00551%	18,139
Admixed American	0.00503%	19,863
African / African-American	0.00401%	24,957

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser948Phe
Coding: c.2843C>T
MANE Select: NM_001286581
dbSNP: rs200183606
Type: single nucleotide variant
Location: chr11:608299 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.11
Residue 948: 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-ser948phe (accessed [today's date]).

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