Is KIZ p.Arg34Ser (c.102A>T) pathogenic?

KIZ p.Arg34Ser (c.102A>T) is classified Uncertain significance in KIZ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.9852); Very rare (popmax 0.0061%, amr).

How common is KIZ p.Arg34Ser (c.102A>T) in the general population?

KIZ p.Arg34Ser (c.102A>T) is very rare (popmax 0.0061%, amr) (gnomAD).

What do computational predictors say about KIZ p.Arg34Ser (c.102A>T)?

AlphaMissense predicts likely pathogenic (score 0.9852) — an in-silico prediction, not a clinical call.

KIZ p.Arg34Ser

c.102A>T · rs749951530 · VCV1053715

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9852 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0061%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.9852	likely pathogenic · top 1% in KIZ
SaProt	LLR -9.43	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 120 kb · p 0.9 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0061% Admixed American · 3/49,154 alleles

Filtering AF 0.00264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00234%

Overall 0.00296% 41/1,383,888 alleles · very rare exomes 35/1,231,666 · genomes 6/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0061%	16,385
European (non-Finnish)	0.0036%	27,764
Remaining individualsnot grpmax-eligible	0.00184%	54,392
African / African-American	0.00144%	69,584

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: KIZ
Protein: p.Arg34Ser
Coding: c.102A>T
MANE Select: NM_018474
dbSNP: rs749951530
Type: single nucleotide variant
Location: chr20:21132109 (GRCh38)
Gene constraint: LOEUF 1.227 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.82

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

Similar variants

KIZ c.1447-2A>G Likely pathogenic ★★ same type
KIZ c.1612+2T>G Likely pathogenic ★★ same type
KIZ p.Arg195Ter Pathogenic/Likely pathogenic ★★ same type
KIZ p.Arg76Ter Pathogenic ★★ same type
KIZ p.Gln199Ter Pathogenic/Likely pathogenic ★★ same type
KIZ p.Gln22Ter Pathogenic/Likely pathogenic ★★ same type
KIZ p.Glu18Ter Pathogenic/Likely pathogenic ★★ same type
KIZ p.Leu625Ter Pathogenic/Likely pathogenic ★★ 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/kiz-p-arg34ser (accessed [today's date]).

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