Is CIMIP4 p.Phe41Leu (c.121T>C) pathogenic?

CIMIP4 p.Phe41Leu (c.121T>C) is classified Uncertain significance in CIMIP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). AlphaMissense: ambiguous (0.549); Absent from gnomAD v4.1.

How common is CIMIP4 p.Phe41Leu (c.121T>C) in the general population?

CIMIP4 p.Phe41Leu (c.121T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIMIP4 p.Phe41Leu (c.121T>C)?

AlphaMissense predicts ambiguous (score 0.549) — an in-silico prediction, not a clinical call.

CIMIP4 p.Phe41Leu

c.121T>C · rs2518057357 · VCV3235379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.549 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.549	ambiguous
REVEL	0.032	moderately benign-leaning
SaProt	LLR -4.46	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.57	GERP -2.8
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.24 · regional, not allelic
Overall
CADD	13.44	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CIMIP4
Protein: p.Phe41Leu
Coding: c.121T>C
MANE Select: NM_001163857
dbSNP: rs2518057357
Type: single nucleotide variant
Location: chr22:37002205 (GRCh38)
Structure: AlphaFold pLDDT 60.78
Residue 41: the 'disordered' region

Full CIMIP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMIP4 p.Asn260Lys Uncertain significance ★★ ⚠ same type
CIMIP4 p.Ala107Val Uncertain significance ★ ⚠ same type
CIMIP4 p.Ala256Val Uncertain significance ★ ⚠ same type
CIMIP4 p.Ala31Val Uncertain significance ★ ⚠ same type
CIMIP4 p.Ala96Val Uncertain significance ★ ⚠ same type
CIMIP4 p.Arg206Gln Uncertain significance ★ ⚠ same type
CIMIP4 p.Arg206Trp Uncertain significance ★ ⚠ same type
CIMIP4 p.Arg250Trp 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/cimip4-p-phe41leu (accessed [today's date]).

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