Is APH1B p.Phe34= (c.102C>T) pathogenic?

APH1B p.Phe34= (c.102C>T) is classified Likely benign in APH1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). Very rare (popmax 0.0011%, sas).

How common is APH1B p.Phe34= (c.102C>T) in the general population?

APH1B p.Phe34= (c.102C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

APH1B p.Phe34=

c.102C>T · VCV3389277

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.91, phastCons 1
Overall
CADD	15.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,936 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,610,762 alleles · very rare exomes 4/1,458,804 · genomes 1/151,958 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,306
South Asiangrpmax	0.0011%	90,936
European (non-Finnish)	0.000255%	392,844

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: APH1B
Protein: p.Phe34=
Coding: c.102C>T
MANE Select: NM_031301
Type: single nucleotide variant
Location: chr15:63277725 (GRCh38)
Gene constraint: LOEUF 1.327 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.51 · 2 PDB
Residue 34: an α-helix

Full APH1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APH1B p.Phe34Cys Uncertain significance ★ same residue
APH1B p.Ala4Thr Uncertain significance ★ ⚠ same type
APH1B p.Ala76Gly Uncertain significance ★ ⚠ same type
APH1B p.Asn253Ile Uncertain significance ★ ⚠ same type
APH1B p.Asp179Tyr Uncertain significance ★ ⚠ same type
APH1B p.Gly15Arg Uncertain significance ★ ⚠ same type
APH1B p.Gly174Ser Uncertain significance ★ ⚠ same type
APH1B p.Gly187Asp 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/aph1b-p-phe34 (accessed [today's date]).

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