Is COIL p.Asp101Gly (c.302A>G) pathogenic?

COIL p.Asp101Gly (c.302A>G) is classified Uncertain significance in COIL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.0991); Very rare (popmax 0.00891%, eas).

How common is COIL p.Asp101Gly (c.302A>G) in the general population?

COIL p.Asp101Gly (c.302A>G) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about COIL p.Asp101Gly (c.302A>G)?

AlphaMissense predicts likely benign (score 0.0991) — an in-silico prediction, not a clinical call.

COIL p.Asp101Gly

c.302A>G · VCV3268499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0991	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.42	GERP 1.9
Regional constraint	o/e 0.97	unconstrained · MANE · 22 kb · p 0.47 · regional, not allelic
Overall
CADD	17.14	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 0.00891% East Asian · 4/44,894 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,612,596 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
Admixed American	0.00167%	59,926

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: COIL
Protein: p.Asp101Gly
Coding: c.302A>G
MANE Select: NM_004645
Type: single nucleotide variant
Location: chr17:56950940 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.46

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

Similar variants

COIL p.Glu278= Benign ★★ same type
COIL p.Val145Ile Benign ★★ same type
COIL p.Ala362Ser Uncertain significance ★ ⚠ same type
COIL p.Ala69Thr Uncertain significance ★ ⚠ same type
COIL p.Arg112Trp Uncertain significance ★ ⚠ same type
COIL p.Arg352His Uncertain significance ★ ⚠ same type
COIL p.Arg352Leu Uncertain significance ★ ⚠ same type
COIL p.Arg369Cys 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/coil-p-asp101gly (accessed [today's date]).

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