Is MCIDAS p.Ser265Arg (c.793A>C) pathogenic?

MCIDAS p.Ser265Arg (c.793A>C) is classified Uncertain significance in MCIDAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely pathogenic (0.7158); Very rare (popmax 0.00645%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MCIDAS p.Ser265Arg (c.793A>C)?

MCIDAS p.Ser265Arg (c.793A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MCIDAS p.Ser265Arg (c.793A>C) in the general population?

MCIDAS p.Ser265Arg (c.793A>C) is very rare (popmax 0.00645%, nfe) (gnomAD).

What do computational predictors say about MCIDAS p.Ser265Arg (c.793A>C)?

AlphaMissense predicts likely pathogenic (score 0.7158) — an in-silico prediction, not a clinical call.

MCIDAS p.Ser265Arg

c.793A>C · rs1280513752 · VCV2482379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7158 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00645%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7158	likely pathogenic
REVEL	0.391	indeterminate
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,769 bp · p 0.025 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00645% European (non-Finnish) · 74/1,146,724 alleles

Filtering AF 0.00526% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00501% 77/1,535,776 alleles · very rare exomes 73/1,383,592 · genomes 4/152,184 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00645%	15,496
Remaining individualsnot grpmax-eligible	0.00333%	29,989
African / African-American	0.00137%	73,042

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: MCIDAS
Protein: p.Ser265Arg
Coding: c.793A>C
MANE Select: NM_001190787
dbSNP: rs1280513752
Type: single nucleotide variant
Location: chr5:55220731 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.68 · 1 PDB
Residue 265: the 'necessary and sufficient for proper nuclear localization' region; a UniProt-annotated variant site (in cild42; reduced number of cilia and basal bodies)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MCIDAS p.Ala362Val Uncertain significance ★★ ⚠ same condition
MCIDAS p.Asp141Gly Uncertain significance ★★ ⚠ same condition
MCIDAS p.Pro364Arg Uncertain significance ★★ ⚠ same condition
MCIDAS p.Thr109Met Uncertain significance ★★ ⚠ same condition
MCIDAS p.Thr52Ile Uncertain significance ★★ ⚠ same condition
MCIDAS p.Val122Leu Uncertain significance ★★ ⚠ same condition
MCIDAS p.Ala186Thr Uncertain significance ★ ⚠ same condition
MCIDAS p.Ala273Thr Uncertain significance ★ ⚠ same condition

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/mcidas-p-ser265arg (accessed [today's date]).

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