Is APH1A p.Ser79Phe (c.236C>T) pathogenic?

APH1A p.Ser79Phe (c.236C>T) is classified Uncertain significance in APH1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely pathogenic (0.8407); Absent from gnomAD v4.1.

How common is APH1A p.Ser79Phe (c.236C>T) in the general population?

APH1A p.Ser79Phe (c.236C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APH1A p.Ser79Phe (c.236C>T)?

AlphaMissense predicts likely pathogenic (score 0.8407) — an in-silico prediction, not a clinical call.

APH1A p.Ser79Phe

c.236C>T · VCV3883609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8407 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8407	likely pathogenic
REVEL	0.617	indeterminate
SaProt	LLR -13.13	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 2,677 bp · p 4.4e-07 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APH1A
Protein: p.Ser79Phe
Coding: c.236C>T
MANE Select: NM_001077628
Type: single nucleotide variant
Location: chr1:150268005 (GRCh38)
Gene constraint: LOEUF 0.806 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.69 · 25 PDB
Residue 79: an α-helix

Full APH1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APH1A p.Ala37Ser Uncertain significance ★ ⚠ same type
APH1A p.Ala49Ser Uncertain significance ★ ⚠ same type
APH1A p.Arg109Gly Uncertain significance ★ ⚠ same type
APH1A p.Arg186Trp Uncertain significance ★ ⚠ same type
APH1A p.Arg241Gly Uncertain significance ★ ⚠ same type
APH1A p.Arg241His Uncertain significance ★ ⚠ same type
APH1A p.Arg66Trp Uncertain significance ★ ⚠ same type
APH1A p.Asp61Asn 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/aph1a-p-ser79phe (accessed [today's date]).

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