Is CILP p.Arg448His (c.1343G>A) pathogenic?

CILP p.Arg448His (c.1343G>A) is classified Benign in CILP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-10). AlphaMissense: likely benign (0.0915); Low-frequency (popmax 1.81%, mid); Associated with CILP-related disorder.

What condition is associated with CILP p.Arg448His (c.1343G>A)?

CILP p.Arg448His (c.1343G>A) is associated with CILP-related disorder (ClinVar).

How common is CILP p.Arg448His (c.1343G>A) in the general population?

CILP p.Arg448His (c.1343G>A) is low-frequency (popmax 1.81%, mid) (gnomAD).

What do computational predictors say about CILP p.Arg448His (c.1343G>A)?

AlphaMissense predicts likely benign (score 0.0915) — an in-silico prediction, not a clinical call.

CILP p.Arg448His

c.1343G>A · rs35714337 · VCV3034274

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0915 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.81%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CILP-related disorder

Computational evidence

Protein change
AlphaMissense	0.0915	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -4.90	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 -2.6	GERP -2.7
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.19 · regional, not allelic
Overall
CADD	14.18	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 1.81% Middle Eastern · 110/6,062 alleles

Filtering AF 1.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.44%

Overall 0.153% 2,464/1,614,014 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.81%	55
South Asian	1.07%	94
Remaining individualsnot grpmax-eligible	0.224%	446
Ashkenazi Jewishnot grpmax-eligible	0.145%	689
Admixed American	0.105%	953
European (non-Finnish)	0.0928%	1,078
African / African-American	0.0386%	2,588
Finnishnot grpmax-eligible	0.0125%	7,981
East Asian	0.00668%	14,961

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: CILP
Protein: p.Arg448His
Coding: c.1343G>A
MANE Select: NM_003613
dbSNP: rs35714337
Type: single nucleotide variant
Location: chr15:65198943 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.30

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

Disease context

CILP-related disorder

Similar variants

CILP p.Arg448Cys Uncertain significance ★ ⚠ same residue
CILP p.Arg431Cys Benign ⚠ same condition
CILP p.Asp647= Likely benign same condition
CILP p.Gln979Arg Benign same condition
CILP p.Gly1166Ser Benign same condition
CILP p.Gly69= Likely benign same condition
CILP p.Thr1078= Likely benign same condition
CILP p.Thr486= Likely benign 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/cilp-p-arg448his (accessed [today's date]).

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