Is INHA p.Pro243Arg (c.728C>G) pathogenic?

INHA p.Pro243Arg (c.728C>G) is classified Uncertain significance in INHA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1546); Very rare (popmax 0.00533%, afr).

How common is INHA p.Pro243Arg (c.728C>G) in the general population?

INHA p.Pro243Arg (c.728C>G) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about INHA p.Pro243Arg (c.728C>G)?

AlphaMissense predicts likely benign (score 0.1546) — an in-silico prediction, not a clinical call.

INHA p.Pro243Arg

c.728C>G · rs376758084 · VCV2280251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1546	likely benign
REVEL	0.57	indeterminate
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,148 bp · p 0.17 · regional, not allelic
Overall
CADD	25.1	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 0.00533% African / African-American · 4/75,074 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,266 alleles · very rare exomes 4/1,461,880 · genomes 0/152,386 · joint denominator

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: INHA
Protein: p.Pro243Arg
Coding: c.728C>G
MANE Select: NM_002191
dbSNP: rs376758084
Type: single nucleotide variant
Location: chr2:219575153 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 70.80

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

Similar variants

INHA p.Ala257Thr Benign/Likely benign ★★ same type
INHA p.Gly109= Benign ★★ same type
INHA p.Gly65= Benign/Likely benign ★★ same type
INHA p.Pro166= Likely benign ★★ same type
INHA p.Ala144Val Uncertain significance ★ ⚠ same type
INHA p.Ala207Thr Uncertain significance ★ ⚠ same type
INHA p.Ala45Thr Uncertain significance ★ ⚠ same type
INHA p.Ala63Val 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/inha-p-pro243arg (accessed [today's date]).

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