Is CHN2 p.Pro438Ser (c.1312C>T) pathogenic?

CHN2 p.Pro438Ser (c.1312C>T) is classified Benign in CHN2 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-05-25). AlphaMissense: likely benign (0.163); Low-frequency (popmax 4.76%, afr).

How common is CHN2 p.Pro438Ser (c.1312C>T) in the general population?

CHN2 p.Pro438Ser (c.1312C>T) is low-frequency (popmax 4.76%, afr) (gnomAD).

What do computational predictors say about CHN2 p.Pro438Ser (c.1312C>T)?

AlphaMissense predicts likely benign (score 0.163) — an in-silico prediction, not a clinical call.

CHN2 p.Pro438Ser

c.1312C>T · rs34971642 · VCV776213

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.163 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.76%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.163	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -5.67	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 1.1	GERP -1.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 318 kb · p 0.0002 · regional, not allelic
Overall
CADD	14.62	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 4.76% African / African-American · 3,574/75,006 alleles

Filtering AF 4.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.58%

Overall 0.253% 4,083/1,614,034 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.76%	21
Admixed American	0.362%	277
Remaining individualsnot grpmax-eligible	0.309%	324
Middle Eastern	0.115%	866
South Asian	0.0121%	8,280
European (non-Finnish)	0.00686%	14,567

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: CHN2
Protein: p.Pro438Ser
Coding: c.1312C>T
MANE Select: NM_004067
dbSNP: rs34971642
Type: single nucleotide variant
Location: chr7:29512640 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 438: a UniProt-annotated variant site (in); the rho-gap domain

Full CHN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHN2 p.Ala201Val Uncertain significance ★ ⚠ same type
CHN2 p.Ala3Thr Uncertain significance ★ ⚠ same type
CHN2 p.Arg290Ser Uncertain significance ★ ⚠ same type
CHN2 p.Arg299Gln Uncertain significance ★ ⚠ same type
CHN2 p.Arg313Thr Uncertain significance ★ ⚠ same type
CHN2 p.Arg39His Uncertain significance ★ ⚠ same type
CHN2 p.Arg404Trp Uncertain significance ★ ⚠ same type
CHN2 p.Arg47Gln 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/chn2-p-pro438ser (accessed [today's date]).

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