Is PKHD1 p.Ser95Phe (c.284C>T) pathogenic?

PKHD1 p.Ser95Phe (c.284C>T) is classified Uncertain significance in PKHD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.1646); Very rare (popmax 0.000617%, nfe); Associated with PKHD1-related disorder.

What condition is associated with PKHD1 p.Ser95Phe (c.284C>T)?

PKHD1 p.Ser95Phe (c.284C>T) is associated with PKHD1-related disorder (ClinVar).

How common is PKHD1 p.Ser95Phe (c.284C>T) in the general population?

PKHD1 p.Ser95Phe (c.284C>T) is very rare (popmax 0.000617%, nfe) (gnomAD).

What do computational predictors say about PKHD1 p.Ser95Phe (c.284C>T)?

AlphaMissense predicts likely benign (score 0.1646) — an in-silico prediction, not a clinical call.

PKHD1 p.Ser95Phe

c.284C>T · rs763835920 · VCV3061360

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1646 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000617%, nfe)

Conditions

PKHD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1646	likely benign
REVEL	0.453	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 466 kb · p 0.074 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000617% European (non-Finnish) · 7/1,134,740 alleles

Filtering AF 0.000257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000165%

Overall 0.000511% 8/1,564,398 alleles · very rare exomes 8/1,412,110 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00165%	60,738
European (non-Finnish)grpmax	0.000617%	162,106

Remaining individuals 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: PKHD1
Protein: p.Ser95Phe
Coding: c.284C>T
MANE Select: NM_138694
dbSNP: rs763835920
Type: single nucleotide variant
Location: chr6:52080006 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 95: the ipt/tig 1; atypical domain

Full PKHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PKHD1-related disorder

Similar variants

PKHD1 p.Ser95= Likely benign ★ same residue
PKHD1 c.390+1G>T Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.707+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.7109+3A>C Likely pathogenic ★★ same condition
PKHD1 c.7486+1G>A Likely pathogenic ★★ same condition
PKHD1 c.778+1G>C Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.7911+2T>C Likely pathogenic ★★ same condition
PKHD1 c.8555-2A>C Pathogenic/Likely pathogenic ★★ same condition

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/pkhd1-p-ser95phe (accessed [today's date]).

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