Is KIZ p.Ala554Ser (c.1660G>T) pathogenic?

KIZ p.Ala554Ser (c.1660G>T) is classified Likely benign in KIZ (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-16). AlphaMissense: likely benign (0.101); Rare (popmax 0.353%, sas).

How common is KIZ p.Ala554Ser (c.1660G>T) in the general population?

KIZ p.Ala554Ser (c.1660G>T) is rare (popmax 0.353%, sas) (gnomAD).

What do computational predictors say about KIZ p.Ala554Ser (c.1660G>T)?

AlphaMissense predicts likely benign (score 0.101) — an in-silico prediction, not a clinical call.

KIZ p.Ala554Ser

c.1660G>T · rs532984240 · VCV1206287

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.101 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.353%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.101	likely benign
SaProt	LLR -5.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.61	GERP -2.4
Regional constraint	o/e 1.00	unconstrained · MANE · 120 kb · p 0.9 · regional, not allelic
Overall
CADD	5.271	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 0.353% South Asian · 318/89,990 alleles

Filtering AF 0.321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.309%

Overall 0.0209% 335/1,605,050 alleles · rare exomes 323/1,452,760 · genomes 12/152,290 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.353%	283
Middle Eastern	0.0331%	3,025
Remaining individualsnot grpmax-eligible	0.0225%	4,436
European (non-Finnish)	8.52e-05%	1,173,428

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.Ala554Ser
Coding: c.1660G>T
MANE Select: NM_018474
dbSNP: rs532984240
Type: single nucleotide variant
Location: chr20:21215630 (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 p.Ala554= Likely benign ★ same residue
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

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-ala554ser (accessed [today's date]).

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