Is INHA p.Arg247Ser (c.739C>A) pathogenic?

INHA p.Arg247Ser (c.739C>A) is classified Uncertain significance in INHA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.2257); Very rare (popmax 0.00666%, amr).

How common is INHA p.Arg247Ser (c.739C>A) in the general population?

INHA p.Arg247Ser (c.739C>A) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about INHA p.Arg247Ser (c.739C>A)?

AlphaMissense predicts likely benign (score 0.2257) — an in-silico prediction, not a clinical call.

INHA p.Arg247Ser

c.739C>A · VCV4038648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2257 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2257	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -5.27	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 3.3	GERP 0.64, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,148 bp · p 0.17 · regional, not allelic
Overall
CADD	18.68	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 0.00666% Admixed American · 4/60,016 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000805% 13/1,614,128 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,004
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.000593%	168,578

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.Arg247Ser
Coding: c.739C>A
MANE Select: NM_002191
Type: single nucleotide variant
Location: chr2:219575164 (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.Arg247His Uncertain significance ★ ⚠ same residue
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

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-arg247ser (accessed [today's date]).

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