Is GDAP1 p.Pro144Ser (c.430C>T) pathogenic?

GDAP1 p.Pro144Ser (c.430C>T) is classified Uncertain significance in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-10). AlphaMissense: likely pathogenic (0.7807); Very rare (popmax 0.008%, afr); Associated with Inborn genetic diseases.

What condition is associated with GDAP1 p.Pro144Ser (c.430C>T)?

GDAP1 p.Pro144Ser (c.430C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GDAP1 p.Pro144Ser (c.430C>T) in the general population?

GDAP1 p.Pro144Ser (c.430C>T) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about GDAP1 p.Pro144Ser (c.430C>T)?

AlphaMissense predicts likely pathogenic (score 0.7807) — an in-silico prediction, not a clinical call.

GDAP1 p.Pro144Ser

c.430C>T · VCV4857907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7807 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7807	likely pathogenic
REVEL	0.803	moderately pathogenic-leaning
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.0041 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.008% African / African-American · 6/75,012 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000558% 9/1,613,888 alleles · very rare exomes 5/1,461,672 · genomes 4/152,216 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.008%	12,502
Admixed American	0.00333%	30,007
South Asian	0.0011%	91,060

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: GDAP1
Protein: p.Pro144Ser
Coding: c.430C>T
MANE Select: NM_018972
Type: single nucleotide variant
Location: chr8:74360256 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 144: an α-helix

Full GDAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GDAP1 p.Pro144Leu Likely pathogenic ★ same residue
GDAP1 p.Pro144Thr Uncertain significance ★ ⚠ same residue
GDAP1 p.Arg282His Pathogenic ★★ ⚠ same condition
GDAP1 c.694+5G>A Uncertain significance ★★ same condition
GDAP1 p.Ala20Thr Uncertain significance ★★ ⚠ same condition
GDAP1 p.Arg108Gly Uncertain significance ★★ ⚠ same condition
GDAP1 p.Asn227Lys Uncertain significance ★★ ⚠ same condition
GDAP1 p.Asn298His Uncertain significance ★★ ⚠ same condition

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/gdap1-p-pro144ser (accessed [today's date]).

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