Is IQCH p.Pro10Ser (c.28C>T) pathogenic?

IQCH p.Pro10Ser (c.28C>T) is classified Uncertain significance in IQCH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-11). AlphaMissense: likely benign (0.1994); Very rare (popmax 0.00271%, nfe).

How common is IQCH p.Pro10Ser (c.28C>T) in the general population?

IQCH p.Pro10Ser (c.28C>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about IQCH p.Pro10Ser (c.28C>T)?

AlphaMissense predicts likely benign (score 0.1994) — an in-silico prediction, not a clinical call.

IQCH p.Pro10Ser

c.28C>T · rs377745050 · VCV2388371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1994	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -5.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.7	GERP 1, phastCons 1
Overall
CADD	21.8	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

Grpmax group 0.00271% European (non-Finnish) · 32/1,179,816 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00204% 33/1,613,692 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,869
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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: IQCH
Protein: p.Pro10Ser
Coding: c.28C>T
MANE Select: NM_024666 · reported on NM_001031715
dbSNP: rs377745050
Type: single nucleotide variant
Location: chr15:67254924 (GRCh38)

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

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-pro10ser (accessed [today's date]).

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