Is CLGN p.Phe3Ile (c.7T>A) pathogenic?

CLGN p.Phe3Ile (c.7T>A) is classified Uncertain significance in CLGN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely benign (0.0748); Absent from gnomAD v4.1.

How common is CLGN p.Phe3Ile (c.7T>A) in the general population?

CLGN p.Phe3Ile (c.7T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLGN p.Phe3Ile (c.7T>A)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

CLGN p.Phe3Ile

c.7T>A · rs2546268448 · VCV3145739

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -7.10	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	GERP 3.6, phastCons 0.97
Regional constraint	o/e 0.90	unconstrained · MANE · 24 kb · p 0.01 · regional, not allelic
Overall
CADD	18.66	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLGN
Protein: p.Phe3Ile
Coding: c.7T>A
MANE Select: NM_004362
dbSNP: rs2546268448
Type: single nucleotide variant
Location: chr4:140413072 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.36

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

Similar variants

CLGN p.Ala210Thr Uncertain significance ★ ⚠ same type
CLGN p.Ala529Thr Uncertain significance ★ ⚠ same type
CLGN p.Ala63Gly Uncertain significance ★ ⚠ same type
CLGN p.Arg196Gly Uncertain significance ★ ⚠ same type
CLGN p.Arg373Ser Uncertain significance ★ ⚠ same type
CLGN p.Arg603His Uncertain significance ★ ⚠ same type
CLGN p.Arg608Gln Uncertain significance ★ ⚠ same type
CLGN p.Arg70Thr 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/clgn-p-phe3ile (accessed [today's date]).

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