Is CLGN p.Thr162Ile (c.485C>T) pathogenic?

CLGN p.Thr162Ile (c.485C>T) is classified Uncertain significance in CLGN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely benign (0.165); Ultra-rare (popmax 0.0372%, afr).

How common is CLGN p.Thr162Ile (c.485C>T) in the general population?

CLGN p.Thr162Ile (c.485C>T) is ultra-rare (popmax 0.0372%, afr) (gnomAD).

What do computational predictors say about CLGN p.Thr162Ile (c.485C>T)?

AlphaMissense predicts likely benign (score 0.165) — an in-silico prediction, not a clinical call.

CLGN p.Thr162Ile

c.485C>T · VCV3833957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.165 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0372%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.165	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -8.54	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 6.3	GERP 6.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 24 kb · p 0.01 · regional, not allelic
Overall
CADD	24.8	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 0.0372% African / African-American · 27/72,538 alleles

Filtering AF 0.0262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0226%

Overall 0.00463% 72/1,554,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0372%	2,687
European (non-Finnish)	0.00385%	25,967
Remaining individualsnot grpmax-eligible	0.00166%	60,200

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: CLGN
Protein: p.Thr162Ile
Coding: c.485C>T
MANE Select: NM_004362
Type: single nucleotide variant
Location: chr4:140402001 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.36
Residue 162: a disulfide bond

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-thr162ile (accessed [today's date]).

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