Is CIMAP1B p.Ala134Val (c.401C>T) pathogenic?

CIMAP1B p.Ala134Val (c.401C>T) is classified Uncertain significance in CIMAP1B (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-07). AlphaMissense: likely benign (0.0743); Ultra-rare (popmax 0.0494%, mid).

How common is CIMAP1B p.Ala134Val (c.401C>T) in the general population?

CIMAP1B p.Ala134Val (c.401C>T) is ultra-rare (popmax 0.0494%, mid) (gnomAD).

What do computational predictors say about CIMAP1B p.Ala134Val (c.401C>T)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

CIMAP1B p.Ala134Val

c.401C>T · rs202039189 · VCV3235440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -7.31	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 -0.12	GERP -4.5
Regional constraint	o/e 1.07	unconstrained · MANE · 1,594 bp · p 0.18 · regional, not allelic
Overall
CADD	1.243	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 0.0494% Middle Eastern · 3/6,076 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.022% 354/1,612,492 alleles · ultra-rare exomes 310/1,460,326 · genomes 44/152,166 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.112%	890
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,479
Middle Easterngrpmax	0.0494%	2,025
Admixed American	0.035%	2,854
Remaining individualsnot grpmax-eligible	0.0272%	3,673
European (non-Finnish)	0.0187%	5,337
South Asian	0.0011%	91,054

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CIMAP1B
Protein: p.Ala134Val
Coding: c.401C>T
MANE Select: NM_001014440
dbSNP: rs202039189
Type: single nucleotide variant
Location: chr22:50531208 (GRCh38)
Structure: AlphaFold pLDDT 73.82

Full CIMAP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1B p.Ala134Glu Uncertain significance ★ ⚠ same residue
CIMAP1B p.Ala143Val Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala245Thr Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala39Thr Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala84Ser Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala97Val Uncertain significance ★ ⚠ same type
CIMAP1B p.Arg16Cys Uncertain significance ★ same type
CIMAP1B p.Arg207Gln 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/cimap1b-p-ala134val (accessed [today's date]).

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