Is CILP p.Arg173His (c.518G>A) pathogenic?

CILP p.Arg173His (c.518G>A) is classified Uncertain significance in CILP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: ambiguous (0.4911); Ultra-rare (popmax 0.0227%, afr).

How common is CILP p.Arg173His (c.518G>A) in the general population?

CILP p.Arg173His (c.518G>A) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about CILP p.Arg173His (c.518G>A)?

AlphaMissense predicts ambiguous (score 0.4911) — an in-silico prediction, not a clinical call.

CILP p.Arg173His

c.518G>A · rs369581577 · VCV3145030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4911 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4911	ambiguous
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -10.52	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.19 · regional, not allelic
Overall
CADD	34.0	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 0.0227% African / African-American · 17/74,918 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00186% 30/1,613,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,407
South Asian	0.00329%	30,363
Finnishnot grpmax-eligible	0.00156%	63,952
European (non-Finnish)	0.000763%	131,116

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.Arg173His
Coding: c.518G>A
MANE Select: NM_003613
dbSNP: rs369581577
Type: single nucleotide variant
Location: chr15:65205373 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.30
Residue 173: a disulfide bond; the tsp type-1 domain

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

Similar variants

CILP p.Leu1064= Benign ★★ same type
CILP p.Ala1003Asp Uncertain significance ★ ⚠ same type
CILP p.Ala102Val Uncertain significance ★ ⚠ same type
CILP p.Ala1053Thr Uncertain significance ★ ⚠ same type
CILP p.Ala1091Thr Uncertain significance ★ ⚠ same type
CILP p.Ala1091Val Uncertain significance ★ ⚠ same type
CILP p.Ala1114Gly Uncertain significance ★ ⚠ same type
CILP p.Ala1143Thr 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/cilp-p-arg173his (accessed [today's date]).

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