Is CLGN p.Asp147Val (c.440A>T) pathogenic?

CLGN p.Asp147Val (c.440A>T) is classified Uncertain significance in CLGN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.1275); Rare (popmax 0.439%, afr).

How common is CLGN p.Asp147Val (c.440A>T) in the general population?

CLGN p.Asp147Val (c.440A>T) is rare (popmax 0.439%, afr) (gnomAD).

What do computational predictors say about CLGN p.Asp147Val (c.440A>T)?

AlphaMissense predicts likely benign (score 0.1275) — an in-silico prediction, not a clinical call.

CLGN p.Asp147Val

c.440A>T · VCV4229826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1275 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.439%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1275	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	acceptor loss · deltas
Pangolin	Δ0.20	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 6.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 24 kb · p 0.01 · regional, not allelic
Overall
CADD	26.3	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 0.439% African / African-American · 322/73,388 alleles

Filtering AF 0.399% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.384%

Overall 0.0225% 355/1,575,156 alleles · rare exomes 157/1,423,082 · genomes 198/152,074 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.439%	228
Middle Eastern	0.0336%	2,980
Remaining individualsnot grpmax-eligible	0.0328%	3,046
Admixed American	0.00893%	11,200
South Asian	0.00351%	28,454
European (non-Finnish)	0.000259%	385,539

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.Asp147Val
Coding: c.440A>T
MANE Select: NM_004362
Type: single nucleotide variant
Location: chr4:140402046 (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-asp147val (accessed [today's date]).

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