Is IQCH p.Ser142Phe (c.425C>T) pathogenic?

IQCH p.Ser142Phe (c.425C>T) is classified Uncertain significance in IQCH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.1492); Absent from gnomAD v4.1.

How common is IQCH p.Ser142Phe (c.425C>T) in the general population?

IQCH p.Ser142Phe (c.425C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IQCH p.Ser142Phe (c.425C>T)?

AlphaMissense predicts likely benign (score 0.1492) — an in-silico prediction, not a clinical call.

IQCH p.Ser142Phe

c.425C>T · VCV4276345

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1492 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1492	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -8.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.42, phastCons 0.94
Overall
CADD	19.27	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

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: IQCH
Protein: p.Ser142Phe
Coding: c.425C>T
MANE Select: NM_001031715
Type: single nucleotide variant
Location: chr15:67337012 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.09

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

Similar variants

IQCH p.Val305= Benign ★★ same type
IQCH p.Ala539Thr Uncertain significance ★ ⚠ same type
IQCH p.Ala588Thr Uncertain significance ★ ⚠ same type
IQCH p.Ala711Val Uncertain significance ★ ⚠ same type
IQCH p.Ala718Thr Uncertain significance ★ ⚠ same type
IQCH p.Ala809Gly Uncertain significance ★ ⚠ same type
IQCH p.Arg177Gln Uncertain significance ★ ⚠ same type
IQCH p.Arg207Cys 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/iqch-p-ser142phe (accessed [today's date]).

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