Is CIMAP1D p.Ser265Trp (c.794C>G) pathogenic?

CIMAP1D p.Ser265Trp (c.794C>G) is classified Uncertain significance in CIMAP1D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.323); Ultra-rare (popmax 0.0339%, mid).

How common is CIMAP1D p.Ser265Trp (c.794C>G) in the general population?

CIMAP1D p.Ser265Trp (c.794C>G) is ultra-rare (popmax 0.0339%, mid) (gnomAD).

What do computational predictors say about CIMAP1D p.Ser265Trp (c.794C>G)?

AlphaMissense predicts likely benign (score 0.323) — an in-silico prediction, not a clinical call.

CIMAP1D p.Ser265Trp

c.794C>G · VCV4003067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.323 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0339%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.323	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -9.07	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 6.3	GERP 0.97, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.28 · regional, not allelic
Overall
CADD	23.2	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 0.0339% Middle Eastern · 2/5,900 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00247%

Overall 0.00192% 31/1,611,434 alleles · ultra-rare exomes 29/1,459,228 · genomes 2/152,206 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0339%	2,950
Remaining individualsnot grpmax-eligible	0.00321%	31,180
European (non-Finnish)	0.00229%	43,685

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: CIMAP1D
Protein: p.Ser265Trp
Coding: c.794C>G
MANE Select: NM_182577
Type: single nucleotide variant
Location: chr19:463920 (GRCh38)
Structure: AlphaFold pLDDT 67.70
Residue 265: the 'disordered' region

Full CIMAP1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1D p.Ser265Leu Uncertain significance ★ ⚠ same residue
CIMAP1D p.Ala255Ser Uncertain significance ★ ⚠ same type
CIMAP1D p.Ala66Thr Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg101Cys Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg11Gln Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg11Trp Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg136His Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg138Trp 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/cimap1d-p-ser265trp (accessed [today's date]).

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