Is COIL p.Phe340Tyr (c.1019T>A) pathogenic?

COIL p.Phe340Tyr (c.1019T>A) is classified Uncertain significance in COIL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.1105); Ultra-rare (popmax 0.0178%, eas).

How common is COIL p.Phe340Tyr (c.1019T>A) in the general population?

COIL p.Phe340Tyr (c.1019T>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about COIL p.Phe340Tyr (c.1019T>A)?

AlphaMissense predicts likely benign (score 0.1105) — an in-silico prediction, not a clinical call.

COIL p.Phe340Tyr

c.1019T>A · rs760017532 · VCV3147145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1105 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1105	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.90	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 1.4	GERP -2.4, phastCons 0.014
Regional constraint	o/e 0.97	unconstrained · MANE · 22 kb · p 0.47 · regional, not allelic
Overall
CADD	11.71	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 0.0178% East Asian · 8/44,882 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000547% 8/1,461,884 alleles · ultra-rare

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.Phe340Tyr
Coding: c.1019T>A
MANE Select: NM_004645
dbSNP: rs760017532
Type: single nucleotide variant
Location: chr17:56950223 (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-phe340tyr (accessed [today's date]).

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