Is P4HTM p.Arg201His (c.602G>A) pathogenic?

P4HTM p.Arg201His (c.602G>A) is classified Likely benign in P4HTM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0547); Rare (popmax 0.116%, eas); Associated with Inborn genetic diseases.

What condition is associated with P4HTM p.Arg201His (c.602G>A)?

P4HTM p.Arg201His (c.602G>A) is associated with Inborn genetic diseases (ClinVar).

How common is P4HTM p.Arg201His (c.602G>A) in the general population?

P4HTM p.Arg201His (c.602G>A) is rare (popmax 0.116%, eas) (gnomAD).

What do computational predictors say about P4HTM p.Arg201His (c.602G>A)?

AlphaMissense predicts likely benign (score 0.0547) — an in-silico prediction, not a clinical call.

P4HTM p.Arg201His

c.602G>A · VCV4129879

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0547 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0547	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.87	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 -5.5
Regional constraint	o/e 0.80	unconstrained · MANE · 17 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	2.203	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 0.116% East Asian · 52/44,844 alleles

Filtering AF 0.0907% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0818%

Overall 0.00447% 72/1,611,916 alleles · rare exomes 69/1,459,720 · genomes 3/152,196 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.116%	862
Admixed American	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,416
European (non-Finnish)	0.00136%	73,667
African / African-American	0.00133%	74,908
South Asian	0.0011%	91,050

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: P4HTM
Protein: p.Arg201His
Coding: c.602G>A
MANE Select: NM_177939
Type: single nucleotide variant
Location: chr3:49001603 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 1 PDB
Residue 201: the ef-hand 1 domain

Full P4HTM 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

P4HTM p.Arg201Cys Uncertain significance ★ ⚠ same residue
P4HTM p.Ala233Thr Uncertain significance ★★ ⚠ same condition
P4HTM p.Arg493Gln Uncertain significance ★★ ⚠ same condition
P4HTM p.Ser171Gly Uncertain significance ★★ ⚠ same condition
P4HTM p.Ser184Thr Uncertain significance ★★ ⚠ same condition
P4HTM c.1073+105G>A Uncertain significance ★ same condition
P4HTM c.1073+16C>G Uncertain significance ★ same condition
P4HTM c.1073+36T>G Conflicting classifications of pathogenicity ★ 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/p4htm-p-arg201his (accessed [today's date]).

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