Is CILP p.Arg320Gln (c.959G>A) pathogenic?

CILP p.Arg320Gln (c.959G>A) is classified Uncertain significance in CILP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-30). AlphaMissense: likely benign (0.2361); Ultra-rare (popmax 0.035%, amr).

How common is CILP p.Arg320Gln (c.959G>A) in the general population?

CILP p.Arg320Gln (c.959G>A) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about CILP p.Arg320Gln (c.959G>A)?

AlphaMissense predicts likely benign (score 0.2361) — an in-silico prediction, not a clinical call.

CILP p.Arg320Gln

c.959G>A · rs35112728 · VCV3145033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2361 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2361	likely benign
REVEL	0.553	indeterminate
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.20	acceptor loss · deltas
Pangolin	Δ0.22	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.19 · regional, not allelic
Overall
CADD	28.1	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 0.035% Admixed American · 21/60,020 alleles

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

Overall 0.0131% 212/1,612,922 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,858
European (non-Finnish)	0.0139%	7,195
African / African-American	0.0133%	7,500
Remaining individualsnot grpmax-eligible	0.0112%	8,914
South Asian	0.00989%	10,112
East Asian	0.00223%	44,884

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.Arg320Gln
Coding: c.959G>A
MANE Select: NM_003613
dbSNP: rs35112728
Type: single nucleotide variant
Location: chr15:65203431 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.30
Residue 320: the ig-like c2-type domain

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

Similar variants

CILP p.Arg320Trp Uncertain significance ★ ⚠ same residue
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

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-arg320gln (accessed [today's date]).

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