Is MLPH p.Glu391Val (c.1172A>T) pathogenic?

MLPH p.Glu391Val (c.1172A>T) is classified Likely benign in MLPH (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-13). AlphaMissense: likely benign (0.1942); Rare (popmax 0.572%, afr).

How common is MLPH p.Glu391Val (c.1172A>T) in the general population?

MLPH p.Glu391Val (c.1172A>T) is rare (popmax 0.572%, afr) (gnomAD).

What do computational predictors say about MLPH p.Glu391Val (c.1172A>T)?

AlphaMissense predicts likely benign (score 0.1942) — an in-silico prediction, not a clinical call.

MLPH p.Glu391Val

c.1172A>T · rs61736277 · VCV780369

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1942 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.572%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1942	likely benign
REVEL	0.501	indeterminate
SaProt	LLR -8.22	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 2.5	GERP -2, phastCons 0.91
Regional constraint	o/e 0.98	unconstrained · MANE · 60 kb · p 0.54 · regional, not allelic
Overall
CADD	21.7	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 0.572% African / African-American · 429/75,032 alleles

Filtering AF 0.527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.509%

Overall 0.0347% 560/1,613,590 alleles · rare exomes 340/1,461,262 · genomes 220/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.572%	175
Middle Eastern	0.1%	1,000
Remaining individualsnot grpmax-eligible	0.064%	1,562
Admixed American	0.0433%	2,308
European (non-Finnish)	0.00475%	21,069
South Asian	0.00329%	30,351

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: MLPH
Protein: p.Glu391Val
Coding: c.1172A>T
MANE Select: NM_024101
dbSNP: rs61736277
Type: single nucleotide variant
Location: chr2:237540415 (GRCh38)
Gene constraint: LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.58
Residue 391: the 'disordered' region

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

Similar variants

MLPH p.Glu391Lys Likely benign ★★ same residue
MLPH p.Glu391Met Uncertain significance ★★ same residue
MLPH p.Arg35Gln Pathogenic/Likely pathogenic ★★ same type
MLPH p.Arg35Trp Pathogenic/Likely pathogenic ★★ same type
MLPH p.Ala236Thr Uncertain significance ★★ ⚠ same type
MLPH p.Ala520Ser Uncertain significance ★★ ⚠ same type
MLPH p.Arg375Cys Uncertain significance ★★ ⚠ same type
MLPH p.Arg507Trp 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/mlph-p-glu391val (accessed [today's date]).

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